Advantage of rare HLA supertype in HIV disease progression

Elizabeth Trachtenberg, Bette Korber, Cristina Sollars, Thomas B. Kepler, Peter T. Hraber, Elizabeth Hayes, Robert Funkhouser, Michael Fugate, James Theiler, Yen S. Hsu, Kevin Kunstman, Samuel Wu, John Phillip Phair, Henry Erlich, Steven M Wolinsky*

*Corresponding author for this work

Research output: Contribution to journalArticle

255 Scopus citations

Abstract

The highly polymorphic human leukocyte antigen (HLA) class I molecules help to determine the specificity and repertoire of the immune response. The great diversity of these antigen-binding molecules confers differential advantages in responding to pathogens, but presents a major obstacle to distinguishing HLA allele-specific effects. HLA class I supertypes provide a functional classification for the many different HLA alleles that overlap in their peptide-binding specificities. We analyzed the association of these discrete HLA supertypes with HIV disease progression rates in a population of HIV-infected men. We found that HLA supertypes alone and in combination conferred a strong differential advantage in responding to HIV infection, independent of the contribution of single HLA alleles that associate with progression of the disease. The correlation of the frequency of the HLA supertypes with viral load suggests that HIV adapts to the most frequent alleles in the population, providing a selective advantage for those individuals who express rare alleles.

Original languageEnglish (US)
Pages (from-to)928-935
Number of pages8
JournalNature Medicine
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Trachtenberg, E., Korber, B., Sollars, C., Kepler, T. B., Hraber, P. T., Hayes, E., Funkhouser, R., Fugate, M., Theiler, J., Hsu, Y. S., Kunstman, K., Wu, S., Phair, J. P., Erlich, H., & Wolinsky, S. M. (2003). Advantage of rare HLA supertype in HIV disease progression. Nature Medicine, 9(7), 928-935. https://doi.org/10.1038/nm893