A very interesting paper from the new issue of AIDS reports that MHC (HLA) alleles associated with control of HIV replication in humans show significant similarities to chimpanzee MHC. Furthermore, in both cases these alleles predict broad targeting of epitopes in the SIV/HIV Gag protein, echoing a slew of recent studies indicating broad CD8 T cell responses to Gag are critical for efficient immunological control of HIV.
The authors note that “the predicted similarity in binding specificity between chimpanzee and protective HLA molecules clearly supports the hypothesis that the MHC class I repertoire of chimpanzees has been formed under selective pressure induced by an HIV-like virus.” They conclude by stating: “our results indicate that the binding motifs of protective HLA and chimpanzee molecules are directed towards peptides able to elicit effective CD8 T-cell responses against HIV-1 and that similarity to chimpanzee MHC specificity plays a central role in controlling HIV-1 viral load in humans.”
AIDS. 22(11):1299-1303, July 11, 2008.
Hoof, Ilka; Kesmir, Can; Lund, Ole; Nielsen, Morten
Background: Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors.
Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities in their MHC class I repertoire.
Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee.
Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control.