Identification of human CML target. HLA-B locus (B12) antigen variants defined by CTL generated between B locus-identical (B12) responder-stimulator pairs.

Abstract

The genetics of human CML targets were studied by seven CTL generated in combinations iun which the responder/stimulator difference was limited to one (or two) HLA-A, -B, or -C antigens. Unstimulated peripheral blood lymphocytes were used as targets. CTL sensitized against antigens A11, Aw31, or B17 lysed all cells bearing the respective target from a large panel of cells from unrelated individuals. Hence, at least one CTL clone was directed against the HLA antigen molecule. However, all CTL also exerted cross-kill to cells not sharing the stimulating HLA antigen. For two CTL, the target of the cross-kill was not clarified. Five CTL were found where the cross-kill was directed against antigen HLA-B12 (Bw44 and Bw45). All these cTL were generated in R/S pairs identical for B locus antigens (Bw44/Bw35 heterozygotes). The individual CTL lysed different parts of the panel of B12-positive target cells. The interpretation is that these CTL detect subtypes of HLA antigens, but alternative possibilities are also considered. Four B12 subtypes are described, tentatively designated as B12-related CML targets. Identification of HLA-B-related CML targets represent CML "typing" of HLA-antigen differences that were not detected serologically. The subtypes can now be tested for their possible functional significance.