Secondary MLC responses of primed lymphocytes after selective sensitization to non-HLA-D determinants.

Two HLA-B,D-identical siblings, who differed only for the HLA-A region because of a maternal recombinational event, were studied in primary (1 degrees) and secondary (2 degrees) mixed lymphocyte culture (MLC). The HLA-A:B recombinant child did not respond to its HLA-B,D-identical sibling in either 1 degrees or 2 degrees MLC. In the reciprocal combination the non-recombinant child responded only weakly in 1 degrees MLC but responded significantly in 2 degrees MLC to the HLA-A:B recombinant child. Thus, it was possible to selectively prime to a non-HLA-D determinant, which is controlled by a gene located distal to HLA-B. Because this determinant was not present on T-cells, it could be distinguished from the serologically defined antigen controlled by the HLA-A locus. Such primed lymphocytes, as well as lymphocytes primed between HLA-identical siblings, revealed high autologous control responses which were not observed when using lymphocytes primed in conventional one-haplotype combinations. The significant 2 degrees MLC response to autologous cells after sensitization to allogeneic cells may reflect recognition of self antigens and raises the question to what extent genetic similarity between responding and stimulating cells is required in the priming phase to elicit a 2 degrees response to autologous cells.