Genetic Control of the Immune Response to HIV Type 1 Envelope Glycoprotein 120 in Mice: Effects of MHC and Transgenic Human CD4

Abstract

HIV infection elicits a strong immune response to viral proteins, including 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 host genes that may control the strength and breadth of the response to gp120 vaccines. Because of the complexity of the human MHC, we have focused on the response of MHC congenic mice, which share an identical genetic background, differing only in H-2 type. The antibody response to gp120 varied markedly with H-2 type. H-2 ^a and H-2 ^k mice gave consistently 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. Transgenic mice expressing human CD4 gave the same titers as normal H-2-matched controls. MHC-linked genetic control of the quantity and quality of antibodies indicate a requirement for T cell help in producing antibodies to unique and shared determinants of gp120.