Alloantigen recognition: Difference between revisions
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Aloantigen recognition refers to [[immune system]] recognition of genetically encoded [[Polymorphism (biology)|polymorphisms]] among the genetically distinguishable members of same species (self-non-self discrimination). Post-transplant recognition of alloantigens occurs in [[Lymphatic system|secondary lymphoid organs.]] Donor specific [[antigen]]s are recognized by recipient’s [[T cell|T lymphocytes]] and triggers adaptive pro-inflammatory response which consequently leads to rejection of allogenic transplants. Allospecific [[T cell|T lymphocytes]] may be stimulated by three major pathways: direct recognition, indirect recognition or semidirect recognition. The pathway involved in specific cases is dictated by intrinsic and extrinsic factors of [[Allotransplantation|allograft]] and directly influence nature and magnitude of [[T cell|T lymphocytes]] mediated immune response. Furthermore, variant tissues and organs such as skin or cornea or solid organ transplants can be recognized in different pathways and therefore are rejected in different fashion.<ref name=":0">{{ |
Aloantigen recognition refers to [[immune system]] recognition of genetically encoded [[Polymorphism (biology)|polymorphisms]] among the genetically distinguishable members of same species (self-non-self discrimination). Post-transplant recognition of alloantigens occurs in [[Lymphatic system|secondary lymphoid organs.]] Donor specific [[antigen]]s are recognized by recipient’s [[T cell|T lymphocytes]] and triggers adaptive pro-inflammatory response which consequently leads to rejection of allogenic transplants. Allospecific [[T cell|T lymphocytes]] may be stimulated by three major pathways: direct recognition, indirect recognition or semidirect recognition. The pathway involved in specific cases is dictated by intrinsic and extrinsic factors of [[Allotransplantation|allograft]] and directly influence nature and magnitude of [[T cell|T lymphocytes]] mediated immune response. Furthermore, variant tissues and organs such as skin or cornea or solid organ transplants can be recognized in different pathways and therefore are rejected in different fashion.<ref name=":0">{{cite journal | vauthors = Marino J, Paster J, Benichou G | title = Allorecognition by T Lymphocytes and Allograft Rejection | language = English | journal = Frontiers in Immunology | volume = 7 | pages = 582 | date = 2016 | pmid = 28018349 | pmc = 5155009 | doi = 10.3389/fimmu.2016.00582 }}</ref> |
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==Direct alloantigen recognition== |
==Direct alloantigen recognition== |
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Population of [[Antigen-presenting cell|antigen presenting cells]] (APCs) is localized inside donor’s tissues and is co-transferred from donor to recipient via transplant procedure. This population is therefore called “passenger cells”. Short after transplantation to new host these cells (especially [[dendritic cell]]s) leave their intra-graft habitat and migrate through [[lymphatic system]] to regional lymphatic nodes.<ref>{{ |
Population of [[Antigen-presenting cell|antigen presenting cells]] (APCs) is localized inside donor’s tissues and is co-transferred from donor to recipient via transplant procedure. This population is therefore called “passenger cells”. Short after transplantation to new host these cells (especially [[dendritic cell]]s) leave their intra-graft habitat and migrate through [[lymphatic system]] to regional lymphatic nodes.<ref>{{cite journal | vauthors = Brown K, Nowocin AK, Meader L, Edwards LA, Smith RA, Wong W | title = Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts | journal = American Journal of Transplantation | volume = 16 | issue = 4 | pages = 1129–38 | date = April 2016 | pmid = 26799449 | pmc = 4988511 | doi = 10.1111/ajt.13584 }}</ref> Inside the lymphatic nodes these [[dendritic cell]]s are confronted with recipient’s naïve [[T cell|T lymphocytes]] and their contact culminate in recognition of allogenic MHC ([[major histocompatibility complex]])- peptide complex displayed on the surface of the passenger cells. This phenomenon is called direct recognition and leads to acute rejection of allografts mediated by specialized [[T helper cell|CD4+T lymphocytes]] and [[Cytotoxic T cell|CD8+ T lymphocytes]].<ref>{{cite journal | vauthors = Boardman DA, Jacob J, Smyth LA, Lombardi G, Lechler RI | title = What Is Direct Allorecognition? | journal = Current Transplantation Reports | volume = 3 | issue = 4 | pages = 275–283 | date = 2016-12-01 | pmid = 27909647 | pmc = 5107184 | doi = 10.1007/s40472-016-0115-8 }}</ref> |
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In this case, alloreactive T cells are stimulated by donor [[Antigen-presenting cell|APCs]] which express both the allogeneic MHC and costimulatory activity. |
In this case, alloreactive T cells are stimulated by donor [[Antigen-presenting cell|APCs]] which express both the allogeneic MHC and costimulatory activity. |
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== Semi-direct alloantigen recognition (cross-dressing) == |
== Semi-direct alloantigen recognition (cross-dressing) == |
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The third pathway of recognition also involve donor [[Antigen-presenting cell|APCs]], but in this case are their membrane components fused with recipient [[Antigen-presenting cell|APCs]] and therefore can present intact donor MHC molecules to the host.<ref>{{ |
The third pathway of recognition also involve donor [[Antigen-presenting cell|APCs]], but in this case are their membrane components fused with recipient [[Antigen-presenting cell|APCs]] and therefore can present intact donor MHC molecules to the host.<ref>{{cite journal | vauthors = Lin CM, Gill RG | title = Direct and indirect allograft recognition: pathways dictating graft rejection mechanisms | journal = Current Opinion in Organ Transplantation | volume = 21 | issue = 1 | pages = 40–4 | date = February 2016 | pmid = 26575853 | pmc = 4701596 | doi = 10.1097/MOT.0000000000000263 }}</ref> This is possible by unique ability to exchange molecules such as [[RNA]] or proteins which is well established among leukocytes. There are several possibilities how this can be achieved: cell-cell contact ([[trogocytosis]]), nanotubes or release of extracellular vesicles such as [[Exosome (vesicle)|exosomes]]. Myeloid [[Antigen-presenting cell|antigen presenting cell]]<nowiki/>s and [[dendritic cell]]s in particular are one of the major [[Exosome (vesicle)|exosome]] producers. There are known especially for their ability to transport functional MHC molecules with bonded [[antigen]] peptide (pMHC) to different cells population including other [[dendritic cell]]s. In consequence these [[dendritic cell]]s which acquired new pMHC, displayed on their surface, became “cross-dressed”.<ref>{{cite journal | vauthors = Lema DA, Burlingham WJ | title = Role of exosomes in tumour and transplant immune regulation | journal = Scandinavian Journal of Immunology | volume = 90 | issue = 5 | pages = e12807 | date = November 2019 | pmid = 31282004 | doi = 10.1111/sji.12807 }}</ref> This pMHC is capable of normal [[antigen presentation]] to effectors cells. Usually, the mechanism of cross-dressing serves purposes of amplifying [[immune response]] to certain [[antigen]]s, but in case of alloantigen recognition the [[Antigen-presenting cell|APCs]] are able, thanks to this mechanism, to prime both direct and indirect [[T cell|T lymphocytes]] by expressing both self- MHC and allo- MHC peptides derived from donor passenger [[Antigen-presenting cell|APCs]]. Semi-direct alloantigen recognition therefore contributes to acute rejection by eliciting response of specialized [[CD4+ helper cells|CD4+]] and [[Cytotoxic T cell|CD8+]] [[T cell|T lymphocytes]].<ref>{{cite journal | vauthors = Burlingham WJ | title = "Cross-Dressing" Becomes Fashionable Among Transplant Recipients | journal = American Journal of Transplantation | volume = 17 | issue = 1 | pages = 5–6 | date = January 2017 | pmid = 27589607 | doi = 10.1111/ajt.14032 }}</ref> |
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==References== |
== References == |
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{{Reflist}} |
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[[Category:Immune system]] |
[[Category:Immune system]] |
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Revision as of 07:41, 1 February 2020
Aloantigen recognition refers to immune system recognition of genetically encoded polymorphisms among the genetically distinguishable members of same species (self-non-self discrimination). Post-transplant recognition of alloantigens occurs in secondary lymphoid organs. Donor specific antigens are recognized by recipient’s T lymphocytes and triggers adaptive pro-inflammatory response which consequently leads to rejection of allogenic transplants. Allospecific T lymphocytes may be stimulated by three major pathways: direct recognition, indirect recognition or semidirect recognition. The pathway involved in specific cases is dictated by intrinsic and extrinsic factors of allograft and directly influence nature and magnitude of T lymphocytes mediated immune response. Furthermore, variant tissues and organs such as skin or cornea or solid organ transplants can be recognized in different pathways and therefore are rejected in different fashion.[1]
Direct alloantigen recognition
Population of antigen presenting cells (APCs) is localized inside donor’s tissues and is co-transferred from donor to recipient via transplant procedure. This population is therefore called “passenger cells”. Short after transplantation to new host these cells (especially dendritic cells) leave their intra-graft habitat and migrate through lymphatic system to regional lymphatic nodes.[2] Inside the lymphatic nodes these dendritic cells are confronted with recipient’s naïve T lymphocytes and their contact culminate in recognition of allogenic MHC (major histocompatibility complex)- peptide complex displayed on the surface of the passenger cells. This phenomenon is called direct recognition and leads to acute rejection of allografts mediated by specialized CD4+T lymphocytes and CD8+ T lymphocytes.[3]
In this case, alloreactive T cells are stimulated by donor APCs which express both the allogeneic MHC and costimulatory activity.
Indirect alloantigen recognition
Second route of allorecognition mimics normal antigen mechanism of T lymphocytes stimulation by nominal antigens. In this case the alloantigens derived from graft are internalized, processed and presented in form of peptides by recipient’s APCs on their MHC II molecules. Rejection mediated by T lymphocytes sensitized by direct allorecognition pathway is predominant in the short period after the transplantation, but usually subsides with depletion of passenger cells while indirect recognition contributes to continuing graft damage and plays role in chronic rejection.[1]
The main difference between indirect and direct alloantigen recognition stems from the origin of the macrophages (type of APC). In direct alloantigen recognition, the involved dendritic cells are donor derived. In indirect alloantigen recognition, the dendritic cells (APCs) involved are recipient APCs.
Semi-direct alloantigen recognition (cross-dressing)
The third pathway of recognition also involve donor APCs, but in this case are their membrane components fused with recipient APCs and therefore can present intact donor MHC molecules to the host.[4] This is possible by unique ability to exchange molecules such as RNA or proteins which is well established among leukocytes. There are several possibilities how this can be achieved: cell-cell contact (trogocytosis), nanotubes or release of extracellular vesicles such as exosomes. Myeloid antigen presenting cells and dendritic cells in particular are one of the major exosome producers. There are known especially for their ability to transport functional MHC molecules with bonded antigen peptide (pMHC) to different cells population including other dendritic cells. In consequence these dendritic cells which acquired new pMHC, displayed on their surface, became “cross-dressed”.[5] This pMHC is capable of normal antigen presentation to effectors cells. Usually, the mechanism of cross-dressing serves purposes of amplifying immune response to certain antigens, but in case of alloantigen recognition the APCs are able, thanks to this mechanism, to prime both direct and indirect T lymphocytes by expressing both self- MHC and allo- MHC peptides derived from donor passenger APCs. Semi-direct alloantigen recognition therefore contributes to acute rejection by eliciting response of specialized CD4+ and CD8+ T lymphocytes.[6]
References
- ^ a b Marino J, Paster J, Benichou G (2016). "Allorecognition by T Lymphocytes and Allograft Rejection". Frontiers in Immunology. 7: 582. doi:10.3389/fimmu.2016.00582. PMC 5155009. PMID 28018349.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Brown K, Nowocin AK, Meader L, Edwards LA, Smith RA, Wong W (April 2016). "Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts". American Journal of Transplantation. 16 (4): 1129–38. doi:10.1111/ajt.13584. PMC 4988511. PMID 26799449.
- ^ Boardman DA, Jacob J, Smyth LA, Lombardi G, Lechler RI (2016-12-01). "What Is Direct Allorecognition?". Current Transplantation Reports. 3 (4): 275–283. doi:10.1007/s40472-016-0115-8. PMC 5107184. PMID 27909647.
- ^ Lin CM, Gill RG (February 2016). "Direct and indirect allograft recognition: pathways dictating graft rejection mechanisms". Current Opinion in Organ Transplantation. 21 (1): 40–4. doi:10.1097/MOT.0000000000000263. PMC 4701596. PMID 26575853.
- ^ Lema DA, Burlingham WJ (November 2019). "Role of exosomes in tumour and transplant immune regulation". Scandinavian Journal of Immunology. 90 (5): e12807. doi:10.1111/sji.12807. PMID 31282004.
- ^ Burlingham WJ (January 2017). ""Cross-Dressing" Becomes Fashionable Among Transplant Recipients". American Journal of Transplantation. 17 (1): 5–6. doi:10.1111/ajt.14032. PMID 27589607.