To function, CD8 forms a dimer, consisting of a pair of CD8 chains. The most common form of CD8 is composed of a CD8-α and CD8-β chain, both members of the immunoglobulin superfamily with an immunoglobulin variable (IgV)-like extracellular domain connected to the membrane by a thin stalk, and an intracellular tail. Less-common homodimers of the CD8-α chain are also expressed on some cells. The molecular weight of CD8 is about 13,463.2 Da. The structure of the CD8 molecule was determined by Leahy, D.J., Axel, R., and Hendrickson, W.A. by X-ray Diffraction at a 2.6A resolution. The structure was determined to have an immunoglobulin-like beta-sandwich folding and 114 amino acid residues. 2% of the protein is wound into α-helices and 46% into β-sheets, with the remaining 52% of the molecules remaining in the loop portions.
Schematic representation of the heterodimeric CD8 co-receptor
The extracellular IgV-like domain of CD8-α interacts with the α3 portion of the Class I MHC molecule. This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen-specific activation. Cytotoxic T cells with CD8 surface protein are called CD8+ T cells. The main recognition site is a flexible loop at the α3 domain of an MHC molecule. This was discovered by doing mutational analyses. The flexible α3 domain is located between residues 223 and 229 in the genome.
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^Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. p. 73. ISBN1-84110-100-1.
^Devine L, Sun J, Barr M, Kavathas P (1999). "Orientation of the Ig domains of CD8 alpha beta relative to MHC class I". J Immunol162 (2): 846–51. PMID9916707.