Alessandro Sette: Difference between revisions

Add links
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m v2.04b - Bot T20 CW#61 - Fix errors for CW project (Reference before punctuation)
Sscholze (talk | contribs)
23 edits
m added text to research section and references
Line 27: Line 27:
In the mid-80s, at the same time as  [[Paul M. Allen|Paul Allen]] in [[Emil R. Unanue|Emil Unanue]]’s lab, Sette together with Soren Buus in Howard Grey’s lab reported the first direct evidence that [[Major histocompatibility complex|MHC molecules]]’ function is to bind antigenic peptides<ref>{{Cite journal |last1=Buus |first1=S. |last2=Sette |first2=A. |last3=Colon |first3=S. M. |last4=Jenis |first4=D. M. |last5=Grey |first5=H. M. |date=1986-12-26 |title=Isolation and characterization of antigen-Ia complexes involved in T cell recognition |url=https://pubmed.ncbi.nlm.nih.gov/3490919/ |journal=Cell |volume=47 |issue=6 |pages=1071–1077 |doi=10.1016/0092-8674(86)90822-6 |issn=0092-8674 |pmid=3490919|s2cid=53252762 }}</ref><ref>{{Cite journal |last1=Sette |first1=A. |last2=Buus |first2=S. |last3=Colon |first3=S. |last4=Smith |first4=J. A. |last5=Miles |first5=C. |last6=Grey |first6=H. M. |date=July–August 1987 |title=Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells |url=https://pubmed.ncbi.nlm.nih.gov/3497349/ |journal=Nature |volume=328 |issue=6129 |pages=395–399 |doi=10.1038/328395a0 |issn=0028-0836 |pmid=3497349|s2cid=4266071 }}</ref> and present them to the T cell receptor, which triggers a T cell response. Follow-up work explained [[MHC restriction]].<ref>{{Cite journal |last1=Demotz |first1=S. |last2=Grey |first2=H. M. |last3=Sette |first3=A. |date=1990-08-31 |title=The minimal number of class II MHC-antigen complexes needed for T cell activation |url=https://pubmed.ncbi.nlm.nih.gov/2118680/ |journal=Science |volume=249 |issue=4972 |pages=1028–1030 |doi=10.1126/science.2118680 |issn=0036-8075 |pmid=2118680|bibcode=1990Sci...249.1028D }}</ref><ref>{{Cite journal |last1=Sette |first1=A. |last2=Vitiello |first2=A. |last3=Reherman |first3=B. |last4=Fowler |first4=P. |last5=Nayersina |first5=R. |last6=Kast |first6=W. M. |last7=Melief |first7=C. J. |last8=Oseroff |first8=C. |last9=Yuan |first9=L. |last10=Ruppert |first10=J. |last11=Sidney |first11=J. |date=1994-12-15 |title=The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes |url=https://pubmed.ncbi.nlm.nih.gov/7527444/ |journal=Journal of Immunology |volume=153 |issue=12 |pages=5586–5592 |issn=0022-1767 |pmid=7527444}}</ref> In 1989, utilizing an [[Apple IIe]], Sette wrote the first algorithm<ref>{{Cite journal |last=Sette |first=A. |last2=Buus |first2=S. |last3=Appella |first3=E. |last4=Smith |first4=J. A. |last5=Chesnut |first5=R. |last6=Miles |first6=C. |last7=Colon |first7=S. M. |last8=Grey |first8=H. M. |date=May 1989 |title=Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis |url=https://pubmed.ncbi.nlm.nih.gov/2717617/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=86 |issue=9 |pages=3296–3300 |doi=10.1073/pnas.86.9.3296 |issn=0027-8424 |pmid=2717617}}</ref> to predict peptide binding to two murine MHC alleles and over the course of the next 25 years, he defined motifs associated with over one hundred different class I and class II MHC variants expressed in humans, chimps, macaques, gorilla, horse, and mice.<ref>{{Cite journal |last=Peters |first=Bjoern |last2=Nielsen |first2=Morten |last3=Sette |first3=Alessandro |date=2020-04-26 |title=T Cell Epitope Predictions |url=https://pubmed.ncbi.nlm.nih.gov/32045313/ |journal=Annual Review of Immunology |volume=38 |pages=123–145 |doi=10.1146/annurev-immunol-082119-124838 |issn=1545-3278 |pmid=32045313}}</ref><ref>{{Cite journal |last=Sette |first=A. |last2=Buus |first2=S. |last3=Appella |first3=E. |last4=Smith |first4=J. A. |last5=Chesnut |first5=R. |last6=Miles |first6=C. |last7=Colon |first7=S. M. |last8=Grey |first8=H. M. |date=May 1989 |title=Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis |url=https://pubmed.ncbi.nlm.nih.gov/2717617/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=86 |issue=9 |pages=3296–3300 |doi=10.1073/pnas.86.9.3296 |issn=0027-8424 |pmid=2717617}}</ref><ref>{{Cite journal |last=Ruppert |first=J. |last2=Sidney |first2=J. |last3=Celis |first3=E. |last4=Kubo |first4=R. T. |last5=Grey |first5=H. M. |last6=Sette |first6=A. |date=1993-09-10 |title=Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules |url=https://pubmed.ncbi.nlm.nih.gov/8104103/ |journal=Cell |volume=74 |issue=5 |pages=929–937 |doi=10.1016/0092-8674(93)90472-3 |issn=0092-8674 |pmid=8104103}}</ref> He discovered and characterized how MHC variants can be grouped according to broad common functional specificities (MHC supertypes), greatly facilitating epitope classification, characterization and understanding the basic rules of epitope-MHC interactions.<ref>{{Cite journal |last=Sette |first=A. |last2=Sidney |first2=J. |date=August 1998 |title=HLA supertypes and supermotifs: a functional perspective on HLA polymorphism |url=https://pubmed.ncbi.nlm.nih.gov/9722926/ |journal=Current Opinion in Immunology |volume=10 |issue=4 |pages=478–482 |doi=10.1016/s0952-7915(98)80124-6 |issn=0952-7915 |pmid=9722926}}</ref>
In the mid-80s, at the same time as  [[Paul M. Allen|Paul Allen]] in [[Emil R. Unanue|Emil Unanue]]’s lab, Sette together with Soren Buus in Howard Grey’s lab reported the first direct evidence that [[Major histocompatibility complex|MHC molecules]]’ function is to bind antigenic peptides<ref>{{Cite journal |last1=Buus |first1=S. |last2=Sette |first2=A. |last3=Colon |first3=S. M. |last4=Jenis |first4=D. M. |last5=Grey |first5=H. M. |date=1986-12-26 |title=Isolation and characterization of antigen-Ia complexes involved in T cell recognition |url=https://pubmed.ncbi.nlm.nih.gov/3490919/ |journal=Cell |volume=47 |issue=6 |pages=1071–1077 |doi=10.1016/0092-8674(86)90822-6 |issn=0092-8674 |pmid=3490919|s2cid=53252762 }}</ref><ref>{{Cite journal |last1=Sette |first1=A. |last2=Buus |first2=S. |last3=Colon |first3=S. |last4=Smith |first4=J. A. |last5=Miles |first5=C. |last6=Grey |first6=H. M. |date=July–August 1987 |title=Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells |url=https://pubmed.ncbi.nlm.nih.gov/3497349/ |journal=Nature |volume=328 |issue=6129 |pages=395–399 |doi=10.1038/328395a0 |issn=0028-0836 |pmid=3497349|s2cid=4266071 }}</ref> and present them to the T cell receptor, which triggers a T cell response. Follow-up work explained [[MHC restriction]].<ref>{{Cite journal |last1=Demotz |first1=S. |last2=Grey |first2=H. M. |last3=Sette |first3=A. |date=1990-08-31 |title=The minimal number of class II MHC-antigen complexes needed for T cell activation |url=https://pubmed.ncbi.nlm.nih.gov/2118680/ |journal=Science |volume=249 |issue=4972 |pages=1028–1030 |doi=10.1126/science.2118680 |issn=0036-8075 |pmid=2118680|bibcode=1990Sci...249.1028D }}</ref><ref>{{Cite journal |last1=Sette |first1=A. |last2=Vitiello |first2=A. |last3=Reherman |first3=B. |last4=Fowler |first4=P. |last5=Nayersina |first5=R. |last6=Kast |first6=W. M. |last7=Melief |first7=C. J. |last8=Oseroff |first8=C. |last9=Yuan |first9=L. |last10=Ruppert |first10=J. |last11=Sidney |first11=J. |date=1994-12-15 |title=The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes |url=https://pubmed.ncbi.nlm.nih.gov/7527444/ |journal=Journal of Immunology |volume=153 |issue=12 |pages=5586–5592 |issn=0022-1767 |pmid=7527444}}</ref> In 1989, utilizing an [[Apple IIe]], Sette wrote the first algorithm<ref>{{Cite journal |last=Sette |first=A. |last2=Buus |first2=S. |last3=Appella |first3=E. |last4=Smith |first4=J. A. |last5=Chesnut |first5=R. |last6=Miles |first6=C. |last7=Colon |first7=S. M. |last8=Grey |first8=H. M. |date=May 1989 |title=Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis |url=https://pubmed.ncbi.nlm.nih.gov/2717617/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=86 |issue=9 |pages=3296–3300 |doi=10.1073/pnas.86.9.3296 |issn=0027-8424 |pmid=2717617}}</ref> to predict peptide binding to two murine MHC alleles and over the course of the next 25 years, he defined motifs associated with over one hundred different class I and class II MHC variants expressed in humans, chimps, macaques, gorilla, horse, and mice.<ref>{{Cite journal |last=Peters |first=Bjoern |last2=Nielsen |first2=Morten |last3=Sette |first3=Alessandro |date=2020-04-26 |title=T Cell Epitope Predictions |url=https://pubmed.ncbi.nlm.nih.gov/32045313/ |journal=Annual Review of Immunology |volume=38 |pages=123–145 |doi=10.1146/annurev-immunol-082119-124838 |issn=1545-3278 |pmid=32045313}}</ref><ref>{{Cite journal |last=Sette |first=A. |last2=Buus |first2=S. |last3=Appella |first3=E. |last4=Smith |first4=J. A. |last5=Chesnut |first5=R. |last6=Miles |first6=C. |last7=Colon |first7=S. M. |last8=Grey |first8=H. M. |date=May 1989 |title=Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis |url=https://pubmed.ncbi.nlm.nih.gov/2717617/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=86 |issue=9 |pages=3296–3300 |doi=10.1073/pnas.86.9.3296 |issn=0027-8424 |pmid=2717617}}</ref><ref>{{Cite journal |last=Ruppert |first=J. |last2=Sidney |first2=J. |last3=Celis |first3=E. |last4=Kubo |first4=R. T. |last5=Grey |first5=H. M. |last6=Sette |first6=A. |date=1993-09-10 |title=Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules |url=https://pubmed.ncbi.nlm.nih.gov/8104103/ |journal=Cell |volume=74 |issue=5 |pages=929–937 |doi=10.1016/0092-8674(93)90472-3 |issn=0092-8674 |pmid=8104103}}</ref> He discovered and characterized how MHC variants can be grouped according to broad common functional specificities (MHC supertypes), greatly facilitating epitope classification, characterization and understanding the basic rules of epitope-MHC interactions.<ref>{{Cite journal |last=Sette |first=A. |last2=Sidney |first2=J. |date=August 1998 |title=HLA supertypes and supermotifs: a functional perspective on HLA polymorphism |url=https://pubmed.ncbi.nlm.nih.gov/9722926/ |journal=Current Opinion in Immunology |volume=10 |issue=4 |pages=478–482 |doi=10.1016/s0952-7915(98)80124-6 |issn=0952-7915 |pmid=9722926}}</ref>


Contrary to the then wide-held assumption that [[T-cell receptor|T cell receptors (TCR)]] solely function as on/off switches, Sette showed that depending on the affinity of the interaction, TCR engagement could result in inhibition of T cell activation, normal activation, or heteroclitic stimulation and differential signaling, in a mechanism that is known as TCR antagonism<ref>{{Cite journal |last=De Magistris |first=M. T. |last2=Alexander |first2=J. |last3=Coggeshall |first3=M. |last4=Altman |first4=A. |last5=Gaeta |first5=F. C. |last6=Grey |first6=H. M. |last7=Sette |first7=A. |date=1992-02-21 |title=Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor |url=https://pubmed.ncbi.nlm.nih.gov/1739971/ |journal=Cell |volume=68 |issue=4 |pages=625–634 |doi=10.1016/0092-8674(92)90139-4 |issn=0092-8674 |pmid=1739971}}</ref><ref>{{Cite journal |last=Sette |first=A. |last2=Alexander |first2=J. |last3=Ruppert |first3=J. |last4=Snoke |first4=K. |last5=Franco |first5=A. |last6=Ishioka |first6=G. |last7=Grey |first7=H. M. |date=1994 |title=Antigen analogs/MHC complexes as specific T cell receptor antagonists |url=https://pubmed.ncbi.nlm.nih.gov/8011286/ |journal=Annual Review of Immunology |volume=12 |pages=413–431 |doi=10.1146/annurev.iy.12.040194.002213 |issn=0732-0582 |pmid=8011286}}</ref>. This discovery had a profound influence on the understanding of the impact of epitope analogs on antigen recognition, development of more potent cancer antigens, and basic studies on positive and negative selection<ref>{{Cite journal |last=Bertoletti |first=A. |last2=Sette |first2=A. |last3=Chisari |first3=F. V. |last4=Penna |first4=A. |last5=Levrero |first5=M. |last6=De Carli |first6=M. |last7=Fiaccadori |first7=F. |last8=Ferrari |first8=C. |date=1994-06-02 |title=Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells |url=https://pubmed.ncbi.nlm.nih.gov/8196768/ |journal=Nature |volume=369 |issue=6479 |pages=407–410 |doi=10.1038/369407a0 |issn=0028-0836 |pmid=8196768}}</ref><ref>{{Cite journal |last=Parkhurst |first=M. R. |last2=Salgaller |first2=M. L. |last3=Southwood |first3=S. |last4=Robbins |first4=P. F. |last5=Sette |first5=A. |last6=Rosenberg |first6=S. A. |last7=Kawakami |first7=Y. |date=1996-09-15 |title=Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues |url=https://pubmed.ncbi.nlm.nih.gov/8805655/ |journal=Journal of Immunology (Baltimore, Md.: 1950) |volume=157 |issue=6 |pages=2539–2548 |issn=0022-1767 |pmid=8805655}}</ref>. Sette is using epitopes as specific probes to define the understanding of immune responses to many different targets, from infectious diseases such as COVID-19<ref>{{Cite journal |last=Dan |first=Jennifer M. |last2=Mateus |first2=Jose |last3=Kato |first3=Yu |last4=Hastie |first4=Kathryn M. |last5=Yu |first5=Esther Dawen |last6=Faliti |first6=Caterina E. |last7=Grifoni |first7=Alba |last8=Ramirez |first8=Sydney I. |last9=Haupt |first9=Sonya |last10=Frazier |first10=April |last11=Nakao |first11=Catherine |date=2021-02-05 |title=Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection |url=https://pubmed.ncbi.nlm.nih.gov/33408181/ |journal=Science (New York, N.Y.) |volume=371 |issue=6529 |pages=eabf4063 |doi=10.1126/science.abf4063 |issn=1095-9203 |pmc=7919858 |pmid=33408181}}</ref><ref>{{Cite journal |last=Grifoni |first=Alba |last2=Weiskopf |first2=Daniela |last3=Ramirez |first3=Sydney I. |last4=Mateus |first4=Jose |last5=Dan |first5=Jennifer M. |last6=Moderbacher |first6=Carolyn Rydyznski |last7=Rawlings |first7=Stephen A. |last8=Sutherland |first8=Aaron |last9=Premkumar |first9=Lakshmanane |last10=Jadi |first10=Ramesh S. |last11=Marrama |first11=Daniel |date=2020-06-25 |title=Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals |url=https://www.sciencedirect.com/science/article/pii/S0092867420306103 |journal=Cell |language=en |volume=181 |issue=7 |pages=1489–1501.e15 |doi=10.1016/j.cell.2020.05.015 |issn=0092-8674}}</ref>, tuberculosis<ref>{{Cite journal |last=Lindestam Arlehamn |first=Cecilia S. |last2=Gerasimova |first2=Anna |last3=Mele |first3=Federico |last4=Henderson |first4=Ryan |last5=Swann |first5=Justine |last6=Greenbaum |first6=Jason A. |last7=Kim |first7=Yohan |last8=Sidney |first8=John |last9=James |first9=Eddie A. |last10=Taplitz |first10=Randy |last11=McKinney |first11=Denise M. |date=2013-01 |title=Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset |url=https://pubmed.ncbi.nlm.nih.gov/23358848/ |journal=PLoS pathogens |volume=9 |issue=1 |pages=e1003130 |doi=10.1371/journal.ppat.1003130 |issn=1553-7374 |pmc=3554618 |pmid=23358848}}</ref>, whooping cough, dengue<ref>{{Cite journal |last=Weiskopf |first=Daniela |last2=Bangs |first2=Derek J. |last3=Sidney |first3=John |last4=Kolla |first4=Ravi V. |last5=De Silva |first5=Aruna D. |last6=de Silva |first6=Aravinda M. |last7=Crotty |first7=Shane |last8=Peters |first8=Bjoern |last9=Sette |first9=Alessandro |date=2015-08-04 |title=Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity |url=https://pubmed.ncbi.nlm.nih.gov/26195744/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=112 |issue=31 |pages=E4256–4263 |doi=10.1073/pnas.1505956112 |issn=1091-6490 |pmc=4534238 |pmid=26195744}}</ref> or Zika, to allergies and asthma caused by pollens<ref>{{Cite journal |last=Schulten |first=Véronique |last2=Tripple |first2=Victoria |last3=Sidney |first3=John |last4=Greenbaum |first4=Jason |last5=Frazier |first5=April |last6=Alam |first6=Rafeul |last7=Broide |first7=David |last8=Peters |first8=Bjoern |last9=Sette |first9=Alessandro |date=2014-11 |title=Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy |url=https://pubmed.ncbi.nlm.nih.gov/25042980/ |journal=The Journal of Allergy and Clinical Immunology |volume=134 |issue=5 |pages=1076–1083 |doi=10.1016/j.jaci.2014.05.033 |issn=1097-6825 |pmc=4253970 |pmid=25042980}}</ref>, cockroaches and dust mites, to vaccines<ref>{{Cite journal |last=da Silva Antunes |first=Ricardo |last2=Babor |first2=Mariana |last3=Carpenter |first3=Chelsea |last4=Khalil |first4=Natalie |last5=Cortese |first5=Mario |last6=Mentzer |first6=Alexander J. |last7=Seumois |first7=Grégory |last8=Petro |first8=Christopher D. |last9=Purcell |first9=Lisa A. |last10=Vijayanand |first10=Pandurangan |last11=Crotty |first11=Shane |date=2018-08-31 |title=Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters |url=https://pubmed.ncbi.nlm.nih.gov/29920186/ |journal=The Journal of Clinical Investigation |volume=128 |issue=9 |pages=3853–3865 |doi=10.1172/JCI121309 |issn=1558-8238 |pmc=6118631 |pmid=29920186}}</ref>, autoimmunity and neurodegenerative diseases and cancer.
Contrary to the then wide-held assumption that [[T-cell receptor|T cell receptors (TCR)]] solely function as on/off switches, Sette showed that depending on the affinity of the interaction, TCR engagement could result in inhibition of T cell activation, normal activation, or heteroclitic stimulation and differential signaling, in a mechanism that is known as TCR antagonism.<ref>{{Cite journal |last=De Magistris |first=M. T. |last2=Alexander |first2=J. |last3=Coggeshall |first3=M. |last4=Altman |first4=A. |last5=Gaeta |first5=F. C. |last6=Grey |first6=H. M. |last7=Sette |first7=A. |date=1992-02-21 |title=Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor |url=https://pubmed.ncbi.nlm.nih.gov/1739971/ |journal=Cell |volume=68 |issue=4 |pages=625–634 |doi=10.1016/0092-8674(92)90139-4 |issn=0092-8674 |pmid=1739971}}</ref><ref>{{Cite journal |last=Sette |first=A. |last2=Alexander |first2=J. |last3=Ruppert |first3=J. |last4=Snoke |first4=K. |last5=Franco |first5=A. |last6=Ishioka |first6=G. |last7=Grey |first7=H. M. |date=1994 |title=Antigen analogs/MHC complexes as specific T cell receptor antagonists |url=https://pubmed.ncbi.nlm.nih.gov/8011286/ |journal=Annual Review of Immunology |volume=12 |pages=413–431 |doi=10.1146/annurev.iy.12.040194.002213 |issn=0732-0582 |pmid=8011286}}</ref>


==References==
==References==

Revision as of 15:14, 1 June 2022

Alessandro Sette
BornAugust 11, 1960 (1960-08-11) (age 63)
Rome, Italy
Alma materUniversity of Rome
Known forDefining how T cells see antigens

Alessandro Sette is an Italian immunologist. He was born on August 11, 1960, in Rome, Italy, to Pietro Sette, a prominent Italian businessman and politician, and Renata Sette. Sette is a professor at La Jolla Institute for Immunology (LJI). He is an adjunct professor at the University of California, San Diego. Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.[1]

In 1988, Sette moved to San Diego to conduct research at San Diego biotech Cytel. He then co-founded Epimmune. In 2003, Sette joined the faculty of La Jolla Institute for Immunology.[2]

Sette co-leads the Immune Epitope Database (IEDB), an NIAID-funded online database that catalogues epitopes involved in immune system recognition of allergens, infectious diseases, autoantigens, and transplanted tissue in humans and various species.

In 2020, Sette published the first study of SARS-CoV-2 epitopes targeted by the human immune system.[3] He has co-led research into CD8+ and CD4+ T cell responses in COVID-19 patients[4] and studied CD8+ T cell cross-reactivity to SARS-CoV-2 epitopes and other coronaviruses.[5]

Education

Sette received his Laurea in Biological Sciences from the University of Rome, Italy, followed by postdoctoral fellowships in Immunology with Luciano Adorini[6][7] at the C.R.E. Casaccia in Rome, Italy, and Howard Grey[8][9] at the National Jewish Center for Immunology and Respiratory Medicine in Denver, Colorado.

Publications/patents

Sette is a coauthor of over 900 peer-reviewed publications, and is an inventor on 41 US issued patents. He has a H-factor of 170, and is identified by Clarivate as a highly cited researcher.[10]

Research

In the mid-80s, at the same time as  Paul Allen in Emil Unanue’s lab, Sette together with Soren Buus in Howard Grey’s lab reported the first direct evidence that MHC molecules’ function is to bind antigenic peptides[11][12] and present them to the T cell receptor, which triggers a T cell response. Follow-up work explained MHC restriction.[13][14] In 1989, utilizing an Apple IIe, Sette wrote the first algorithm[15] to predict peptide binding to two murine MHC alleles and over the course of the next 25 years, he defined motifs associated with over one hundred different class I and class II MHC variants expressed in humans, chimps, macaques, gorilla, horse, and mice.[16][17][18] He discovered and characterized how MHC variants can be grouped according to broad common functional specificities (MHC supertypes), greatly facilitating epitope classification, characterization and understanding the basic rules of epitope-MHC interactions.[19]

Contrary to the then wide-held assumption that T cell receptors (TCR) solely function as on/off switches, Sette showed that depending on the affinity of the interaction, TCR engagement could result in inhibition of T cell activation, normal activation, or heteroclitic stimulation and differential signaling, in a mechanism that is known as TCR antagonism[20][21]. This discovery had a profound influence on the understanding of the impact of epitope analogs on antigen recognition, development of more potent cancer antigens, and basic studies on positive and negative selection[22][23]. Sette is using epitopes as specific probes to define the understanding of immune responses to many different targets, from infectious diseases such as COVID-19[24][25], tuberculosis[26], whooping cough, dengue[27] or Zika, to allergies and asthma caused by pollens[28], cockroaches and dust mites, to vaccines[29], autoimmunity and neurodegenerative diseases and cancer.

References

  1. ^ "» Sette Lab". www.lji.org. Retrieved January 5, 2021.
  2. ^ Sette, Alessandro (March 28, 2017). "Portrait of an optimist". Human Vaccines & Immunotherapeutics. 13 (6): 1210–1212. doi:10.1080/21645515.2017.1312175. ISSN 2164-5515. PMC 5489282. PMID 28350507.
  3. ^ Grifoni, Alba; Weiskopf, Daniela; Ramirez, Sydney I.; Mateus, Jose; Dan, Jennifer M.; Moderbacher, Carolyn Rydyznski; Rawlings, Stephen A.; Sutherland, Aaron; Premkumar, Lakshmanane; Jadi, Ramesh S.; Marrama, Daniel (June 25, 2020). "Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals". Cell. 181 (7): 1489–1501.e15. doi:10.1016/j.cell.2020.05.015. ISSN 0092-8674. PMC 7237901. PMID 32473127.
  4. ^ Moderbacher, Carolyn Rydyznski; Ramirez, Sydney I.; Dan, Jennifer M.; Grifoni, Alba; Hastie, Kathryn M.; Weiskopf, Daniela; Belanger, Simon; Abbott, Robert K.; Kim, Christina; Choi, Jinyong; Kato, Yu (November 12, 2020). "Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity". Cell. 183 (4): 996–1012.e19. doi:10.1016/j.cell.2020.09.038. ISSN 0092-8674. PMC 7494270. PMID 33010815.
  5. ^ Mateus, Jose; Grifoni, Alba; Tarke, Alison; Sidney, John; Ramirez, Sydney I.; Dan, Jennifer M.; Burger, Zoe C.; Rawlings, Stephen A.; Smith, Davey M.; Phillips, Elizabeth; Mallal, Simon (October 2, 2020). "Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans". Science. 370 (6512): 89–94. Bibcode:2020Sci...370...89M. doi:10.1126/science.abd3871. ISSN 0036-8075. PMC 7574914. PMID 32753554.
  6. ^ Sette, Alessandro; Colizzi, Vittorio; Appella, Ettore; Doria, Gino; Adorini, Luciano (1986). "Analysis of lysozyme-specific immune responses by synthetic peptides. I. Characterization of antibody and T cell-mediated responses to the N-terminal peptide of hen egg-white lysozyme". European Journal of Immunology. 16 (1): 1–6. doi:10.1002/eji.1830160102. PMID 2936608. S2CID 7646979.
  7. ^ Sette, Alessandro; Doria, Gino; Adorini, Luciano (August 1986). "A microcomputer program for hydrophilicity and amphipathicity analysis of protein antigens". Molecular Immunology. 23 (8): 807–810. doi:10.1016/0161-5890(86)90065-9. PMID 2432413.
  8. ^ Buus, S.; Sette, A.; Colon, S. M.; Jenis, D. M.; Grey, H. M. (December 26, 1986). "Isolation and characterization of antigen-Ia complexes involved in T cell recognition". Cell. 47 (6): 1071–1077. doi:10.1016/0092-8674(86)90822-6. ISSN 0092-8674. PMID 3490919. S2CID 53252762.
  9. ^ Sette, A.; Buus, S.; Colon, S.; Smith, J. A.; Miles, C.; Grey, H. M. (July–August 1987). "Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells". Nature. 328 (6129): 395–399. doi:10.1038/328395a0. ISSN 0028-0836. PMID 3497349. S2CID 4266071.
  10. ^ "Alessandro Sette's Publons profile".
  11. ^ Buus, S.; Sette, A.; Colon, S. M.; Jenis, D. M.; Grey, H. M. (December 26, 1986). "Isolation and characterization of antigen-Ia complexes involved in T cell recognition". Cell. 47 (6): 1071–1077. doi:10.1016/0092-8674(86)90822-6. ISSN 0092-8674. PMID 3490919. S2CID 53252762.
  12. ^ Sette, A.; Buus, S.; Colon, S.; Smith, J. A.; Miles, C.; Grey, H. M. (July–August 1987). "Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells". Nature. 328 (6129): 395–399. doi:10.1038/328395a0. ISSN 0028-0836. PMID 3497349. S2CID 4266071.
  13. ^ Demotz, S.; Grey, H. M.; Sette, A. (August 31, 1990). "The minimal number of class II MHC-antigen complexes needed for T cell activation". Science. 249 (4972): 1028–1030. Bibcode:1990Sci...249.1028D. doi:10.1126/science.2118680. ISSN 0036-8075. PMID 2118680.
  14. ^ Sette, A.; Vitiello, A.; Reherman, B.; Fowler, P.; Nayersina, R.; Kast, W. M.; Melief, C. J.; Oseroff, C.; Yuan, L.; Ruppert, J.; Sidney, J. (December 15, 1994). "The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes". Journal of Immunology. 153 (12): 5586–5592. ISSN 0022-1767. PMID 7527444.
  15. ^ Sette, A.; Buus, S.; Appella, E.; Smith, J. A.; Chesnut, R.; Miles, C.; Colon, S. M.; Grey, H. M. (May 1989). "Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3296–3300. doi:10.1073/pnas.86.9.3296. ISSN 0027-8424. PMID 2717617.
  16. ^ Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (April 26, 2020). "T Cell Epitope Predictions". Annual Review of Immunology. 38: 123–145. doi:10.1146/annurev-immunol-082119-124838. ISSN 1545-3278. PMID 32045313.
  17. ^ Sette, A.; Buus, S.; Appella, E.; Smith, J. A.; Chesnut, R.; Miles, C.; Colon, S. M.; Grey, H. M. (May 1989). "Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3296–3300. doi:10.1073/pnas.86.9.3296. ISSN 0027-8424. PMID 2717617.
  18. ^ Ruppert, J.; Sidney, J.; Celis, E.; Kubo, R. T.; Grey, H. M.; Sette, A. (September 10, 1993). "Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules". Cell. 74 (5): 929–937. doi:10.1016/0092-8674(93)90472-3. ISSN 0092-8674. PMID 8104103.
  19. ^ Sette, A.; Sidney, J. (August 1998). "HLA supertypes and supermotifs: a functional perspective on HLA polymorphism". Current Opinion in Immunology. 10 (4): 478–482. doi:10.1016/s0952-7915(98)80124-6. ISSN 0952-7915. PMID 9722926.
  20. ^ De Magistris, M. T.; Alexander, J.; Coggeshall, M.; Altman, A.; Gaeta, F. C.; Grey, H. M.; Sette, A. (February 21, 1992). "Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor". Cell. 68 (4): 625–634. doi:10.1016/0092-8674(92)90139-4. ISSN 0092-8674. PMID 1739971.
  21. ^ Sette, A.; Alexander, J.; Ruppert, J.; Snoke, K.; Franco, A.; Ishioka, G.; Grey, H. M. (1994). "Antigen analogs/MHC complexes as specific T cell receptor antagonists". Annual Review of Immunology. 12: 413–431. doi:10.1146/annurev.iy.12.040194.002213. ISSN 0732-0582. PMID 8011286.
  22. ^ Bertoletti, A.; Sette, A.; Chisari, F. V.; Penna, A.; Levrero, M.; De Carli, M.; Fiaccadori, F.; Ferrari, C. (June 2, 1994). "Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells". Nature. 369 (6479): 407–410. doi:10.1038/369407a0. ISSN 0028-0836. PMID 8196768.
  23. ^ Parkhurst, M. R.; Salgaller, M. L.; Southwood, S.; Robbins, P. F.; Sette, A.; Rosenberg, S. A.; Kawakami, Y. (September 15, 1996). "Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues". Journal of Immunology (Baltimore, Md.: 1950). 157 (6): 2539–2548. ISSN 0022-1767. PMID 8805655.
  24. ^ Dan, Jennifer M.; Mateus, Jose; Kato, Yu; Hastie, Kathryn M.; Yu, Esther Dawen; Faliti, Caterina E.; Grifoni, Alba; Ramirez, Sydney I.; Haupt, Sonya; Frazier, April; Nakao, Catherine (February 5, 2021). "Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection". Science (New York, N.Y.). 371 (6529): eabf4063. doi:10.1126/science.abf4063. ISSN 1095-9203. PMC 7919858. PMID 33408181.
  25. ^ Grifoni, Alba; Weiskopf, Daniela; Ramirez, Sydney I.; Mateus, Jose; Dan, Jennifer M.; Moderbacher, Carolyn Rydyznski; Rawlings, Stephen A.; Sutherland, Aaron; Premkumar, Lakshmanane; Jadi, Ramesh S.; Marrama, Daniel (June 25, 2020). "Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals". Cell. 181 (7): 1489–1501.e15. doi:10.1016/j.cell.2020.05.015. ISSN 0092-8674.
  26. ^ Lindestam Arlehamn, Cecilia S.; Gerasimova, Anna; Mele, Federico; Henderson, Ryan; Swann, Justine; Greenbaum, Jason A.; Kim, Yohan; Sidney, John; James, Eddie A.; Taplitz, Randy; McKinney, Denise M. (2013-01). "Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset". PLoS pathogens. 9 (1): e1003130. doi:10.1371/journal.ppat.1003130. ISSN 1553-7374. PMC 3554618. PMID 23358848. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  27. ^ Weiskopf, Daniela; Bangs, Derek J.; Sidney, John; Kolla, Ravi V.; De Silva, Aruna D.; de Silva, Aravinda M.; Crotty, Shane; Peters, Bjoern; Sette, Alessandro (August 4, 2015). "Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity". Proceedings of the National Academy of Sciences of the United States of America. 112 (31): E4256–4263. doi:10.1073/pnas.1505956112. ISSN 1091-6490. PMC 4534238. PMID 26195744.
  28. ^ Schulten, Véronique; Tripple, Victoria; Sidney, John; Greenbaum, Jason; Frazier, April; Alam, Rafeul; Broide, David; Peters, Bjoern; Sette, Alessandro (2014-11). "Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy". The Journal of Allergy and Clinical Immunology. 134 (5): 1076–1083. doi:10.1016/j.jaci.2014.05.033. ISSN 1097-6825. PMC 4253970. PMID 25042980. {{cite journal}}: Check date values in: |date= (help)
  29. ^ da Silva Antunes, Ricardo; Babor, Mariana; Carpenter, Chelsea; Khalil, Natalie; Cortese, Mario; Mentzer, Alexander J.; Seumois, Grégory; Petro, Christopher D.; Purcell, Lisa A.; Vijayanand, Pandurangan; Crotty, Shane (August 31, 2018). "Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters". The Journal of Clinical Investigation. 128 (9): 3853–3865. doi:10.1172/JCI121309. ISSN 1558-8238. PMC 6118631. PMID 29920186.

External links


Stub icon

This immunology article is a stub. You can help Wikipedia by expanding it.

Flag of United StatesScientist icon Stub icon

This article about an American scientist is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Alessandro_Sette&oldid=1090989313"