AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz.
In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas of HIV-1/SIV(cpz). In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIV(cpz) Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.
de Groot
Natasja G
NG
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands.
Heijmans
Corrine M C
CM
Zoet
Yvonne M
YM
de Ru
Arnoud H
AH
Verreck
Frank A
FA
van Veelen
Peter A
PA
Drijfhout
Jan W
JW
Doxiadis
Gaby G M
GG
Remarque
Edmond J
EJ
Doxiadis
Ilias I N
II
van Rood
Jon J
JJ
Koning
Frits
F
Bontrop
Ronald E
RE
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D005805:Genes, MHC Class I; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics* / Q000276:immunology*; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015683:Gene Products, gag; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; C103707:HLA-B57 antigen; D015395:Histocompatibility Antigens Class I