Genetics of cell-mediated lympholysis (CML) in man

Human cytotoxic lymphocytes (CTL), developed in responder-stimulator combinations incompatible for only one HLA-B antigen, have been used to study the specificity and genetics of target cell determinants. We were able to develop specific CTLs directed against HLA-B7, B8, B27 and Bw44, as defined by standard serological reagents. CTL-anti-B5 and CTL-anti-Bw35 gave a number of false positive reactions. In addition, we have found that specific cytotoxic effector cells can be generated against B27 by sensitization of cells from a B7 donor and vice versa; B7 and B27 can in this way be recognized easily. The data support the view that HLA-B is the target antigen. In addition, population and family studies revealed that extra reactions with CTLs developed in female (parous) responder-male stimulator combinations were due to HLA-restricted H-Y antigen killing. These findings suggest that by selecting responder-stimulator pairs differing for only one antigen at a locus, it should be possible to develop CTLs which will allow recognition of other specificities at the HLA-B locus and other loci.