Avidity dictates the lytic capacity of human cytolytic T lymphocyte clones with similar fine specificity against murine cells expressing HLA-B27 antigen.
The role of the avidity of human CTL in the recognition and lysis of murine P815 cells expressing HLA-B27.1 Ag has been examined. Seven B27-specific alloreactive CTL clones were tested for their ability to lyse a B27.1+-P815 transfectant clone 1-7E, obtained after cotransfection of P815-HTR cells with HLA-B27.1 and human beta 2-microglobulin genes. The expression level of HLA-B27.1 on 1-7E cells was comparable to that on a human lymphoblastoid cell line, as determined by flow cytometry. Of the seven CTL clones used, CTL 1, 26, and 29 displayed the same fine specificity as established with a panel of target cells expressing six structurally different HLA-B27 variants. However, CTL 1 and 29 were of higher avidity than CTL 26, in that the lysis of human target cells by only this latter clone was inhibited by an anti-CD8 mAb. Based on the same criteria, CTL 2, 15, and 48 possessed the same or very similar fine specificity, but CTL 48 was of higher avidity than CTL 2 or 15. The seventh clone, CTL 40, was of a different fine specificity and its lysis of human target cells was also inhibited by the same anti-CD8 mAb. Only those clones whose lysis of human targets could not be inhibited by anti-CD8 antibody were able to lyse the 1-7E murine transfectants. These results indicate that, for human CTL clones with identical or very similar fine specificity, only those of higher avidity are able to lyse P815 murine cells expressing the HLA-B27 antigen. The lysis of HLA-B27.1+-murine transfectants by relevant clones was inhibited by anti-CD8 antibody. This result strongly suggests that the relative contribution of CD8 in stabilizing the interaction between human CTL and HLA-B27+-murine target cells is more significant than with human target cells.
Calvo
V
V
Department of Immunology, Fundación Jiménez Diaz, Madrid, Spain.
Rojo
S
S
Aparicio
P
P
Galocha
B
B
López de Castro
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002448:Cell Adhesion; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D015235:HLA-B Antigens / Q000032:analysis*; D015796:HLA-B27 Antigen; D006801:Humans; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen