Interaction between CD8 and major histocompatibility complex (MHC) class I mediated by multiple contact surfaces that include the alpha 2 and alpha 3 domains of MHC class I.
The cell surface glycoprotein CD8 functions as a coreceptor with the TCR on cytotoxic T lymphocytes. Mutational analysis of the binding site of CD8 for MHC class I predicted that distinct surfaces of CD8 would interact with both the alpha 2 and alpha 3 domains of class I. Using a cell-cell adhesion assay, we identified three residues Q115, D122, and E128 in the alpha 2 domain of class I critical for interaction with CD8. The side chains of these residues point towards a cavity formed by the alpha 1/alpha 2 platform, the alpha 3 domain and beta 2-microglobulin (beta 2m) of class I. These residues were predicted to contact CD8 based on a bivalent model of interaction between one CD8 alpha/alpha homodimer and two MHC class I molecules. These results therefore provide support for the model.
Sun
J
J
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8035, USA.
Leahy
D J
DJ
Kavathas
P B
PB
D000818:Animals; D001665:Binding Sites; D016827:CD8 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D015789:HLA-A2 Antigen / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D001613:beta 2-Microglobulin / Q000378:metabolism
D016827:CD8 Antigens; D018076:DNA, Complementary; D015789:HLA-A2 Antigen; D001613:beta 2-Microglobulin