Differential cytotoxic T-lymphocyte (CTL) responses in HIV-1 immunised sibling chimpanzees with shared MHC haplotypes

Cell mediated immune responses to HIV-1 and CTL responses in particular dif fer dramatically in infected individuals. This may largely be influenced by the immunogenetic differences of different individuals such as those encod ed by the MHC. These differences may be difficult to dissect due to the imm unosuppressive nature of HIV-1 infection itself. In order to reduce the var iables associated with effects of the virus, one recombinant viral antigen was chosen from a particular HIV-1 variant (rgp120 of the clinical isolate HIV-1(W6.1D)). To minimise differences between outbred hosts, we chose two sibling chimpanzees from which the family pedigree and genetic segregation with respect to polymorphic MHC molecules was known. Immunisation induced s trong antigen specific antibody and T-helper immune responses. The magnitud e and persistence of the humoral and T-helper immune responses were compara ble in both chimpanzees. However, CTL responses were only observed in one s ibling. These responses were subsequently mapped to several distinct epitop es. The CTL response to the immunodominant epitope was found to be presente d in the context of a MHC molecule which was shared by both siblings. The a bsence of a CTL response in the other sibling is not yet understood, but co uld not be attributed to MHC alleles that were not shared by these two chim panzees. These findings suggest that other polymorphic immunoregulatory mec hanisms such as those involved in antigen processing and presentation influ ence host CTL responses to HIV-1. (C) 1999 Elsevier Science B.V. All rights reserved.