GENETIC-CONTROL OF THE IMMUNE-RESPONSE TO HIV TYPE-1 ENVELOPE GLYCOPROTEIN-120 IN MICE - EFFECTS OF MHC AND TRANSGENIC HUMAN CD4

HIV infection elicits a strong immune response to viral proteins, incl uding broadly cross-reactive antibodies to envelope glycoprotein 120 ( gp120), However, vaccination with recombinant gp120 generally produces lower titered antibodies with narrow specificity. We have examined ho st genes that may control the strength and breadth of the response to gp120 vaccines. Because of the complexity of the human MHC, we have fo cused on the response of MHC congenic mice, which share an identical g enetic background, differing only in H-2 type. The antibody response t o gp120 varied markedly with H-2 type. H-2(a) and H-2(k) mice gave con sistently high antibody titers, while H-2(s) mice gave 100-fold lower titers, and H-2(b) mice gave low to intermediate responses, Nearly the same genetic control applied for antibodies to both unique and shared determinants and on a variety of different genetic backgrounds, Trans genic mice expressing human CD4 gave the same titers as normal H-2-mat ched controls, MHC-linked genetic control of the quantity and quality of antibodies indicate a requirement for T cell help in producing anti bodies to unique and shared determinants of gp120.