Specificity of anti‐HLA‐B27 cytotoxic T lymphocytes

Abstract

Sub-types of HLA-B27 were detected by cytotoxic T lymphocytes (CTL) generated between HLA-A, -B- and -C-identical B27-positive individuals. The specificity of 6 independent CTL generated by mixed lymphocyte culture (MLC) of HLA-A, -B and -C serologically identical B27-positive responder and stimulator cells is now reported. Three CTL recognize 1 sub-type, and 3 the other. The combined reactivity of all CTL allows unequivocal typing of B27-positive cells for the 2 different sub-types B27K and B27W. The specificity of 2 CTL was analyzed by cold-target inhibition. No further sub-types of HLA-B27 can be detected by the CTL raised in these combinations. The majority of the CTL is directed against the B27 antigens. Extra reactions on B27-negative cells are caused by a subset(s) of CTL recognizing unknown antigens shared between stimulator and target cells. CTL raised by stimulation of HLA-B27-negative responder cells with B27-positive cells of either sub-type lysed all B27-positive target cells indiscriminately. In cold-target inhibition, B27-positive cells, carrying the sub-type of B27 different from that of the stimulator, could not inhibit the lysis of the cells bearing the stimulator sub-type of B27. This indicates the activation, in B27-negative responders, of at least 2 different groups of CTL clones, 1 directed against shared determinants of HLA-B27, and 1 against the HLA-B27 sub-type. Heterogeneity of the HLA-B27 antigen may have implications for studies on the well-known association between this antigen and various diseases.