Genetic control of major histocomp responses to synthetic polypeptide, (human heteropolymer stimulation/Ir gene complementation/poly(L

Vigorous lymphocyte proliferative response to synthetic polypeptides was observed in cells from 50 normal vol- unteers. Results indicated that 64% responded to poly(LHis, LGlu)-poly(DLAla)--poly(LLys) ((H, G)-A--L) and 54% to poly(LTyr, LGlu)-poly(DLAla)--poly(LLys) ((T, G)-A--L). Subjects could be classified into high-, intermediate-, and non-responder pheno- types according to their stimulation indices. Family studies indi- cated that high responses to these antigens are inherited as histo- compatibility antigen gene (HLA)-linked dominant traits. Two matings suggested gene complementation in response to (T, G)-A- -L and (H, G)-A--L. One, with an intra-HLA recombinant off- spring, provided evidence localizing the immune response gene(s) controlling lymphocyte proliferation to (T, G)-A--L and (H, G)-A-- L, presumably the homologue to Ir-1 of mouse, closer to the,HLA- B than to the HLA-D region. The discovery of the major histocompatibility (MHC)-linked