When effector cells were produced by sensitization in vitro with HLA-A- and B-compatible but HLA-D/DR-incompatible stimulator cells, cytotoxicity apparently was directed against a product of genes closely associated with HLA-D. For effective killing to occur with effector cells against certain minor histocompatibility antigens it is necessary that the effector cells and the target cells be matched for HLA-A or B. We have, therefore, investigated whether sharing of HLA-A or B antigens is needed to obatin efficient lysis with effector cells primed against HLA-D. Good killing was observed with effector cells against HLA-D/DRw3 and against HLA-D/DRw4 whether or not the HLA-A or B antigens were matched. The results indicated that compatibility at HLA-A or B is not required for cell-mediated cytotoxicity against a product of the HLA-D region. The HLA-D region appears to code for products that behave as strong histocompatibility antigens that can by themselves cause cell-mediated killing.
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