A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2.
Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.
Salter
R D
RD
Department of Cell Biology, Stanford University, California 94305.
Benjamin
R J
RJ
Wesley
P K
PK
Buxton
S E
SE
Garrett
T P
TP
Clayberger
C
C
Krensky
A M
AM
Norment
A M
AM
Littman
D R
DR
Parham
P
P
D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016827:CD8 Antigens; D002460:Cell Line; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D015394:Molecular Structure; D009154:Mutation; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell