Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection.
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.


CONCLUSIONS
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.
Hoof
Ilka
I
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. ilka@cbs.dtu.dk
Keşmir
Can
C
Lund
Ole
O
Nielsen
Morten
M
D000483:Alleles; D000818:Animals; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000302:isolation & purification*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D002679:Pan troglodytes / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D054301:gag Gene Products, Human Immunodeficiency Virus