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Advantage of rare HLA supertype in HIV disease progression

Nature Medicine volume 9, pages 928–935 (2003)Cite this article

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.

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Figure 1: HLA class I B-supertype genotypes and viral load.
Figure 2: Amino acid frequency and entropy in HIV subtype B.
Figure 3: Correlation between HLA supertype population frequencies and viral load, indicating rare-allele advantage.

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Acknowledgements

We thank M. Vinson, C. Okoye, J. Joffee-Block and P. Otto for technical assistance, and L. Jacobson for discussions of the data. The project was funded by the National Cancer Institute (R01-HD37356 to S.W.), the National Institute of Allergy and Infectious Diseases (P30-CA79458 to S.W.) and the National Institutes of Health (U01-AI-35039 to J.P. and S.W.). Additional support was provided by the Elizabeth Glazer Pediatric AIDS Foundation (R.F. and B.K.), a Los Alamos National Laboratory Program Developmental Award (B.K., M.F. and J.T.), the My Brother Joey Foundation (E.T.) and an anonymous foundation (S.W.).

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Author notes

  1. Elizabeth Trachtenberg and Bette Korber: These authors contributed equally to this work.

Authors and Affiliations

  1. Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, 94609, California, USA

    Elizabeth Trachtenberg, Cristina Sollars, Elizabeth Hayes, Yen S Hsu & Henry Erlich

  2. Los Alamos National Laboratory, Los Alamos, 87545, New Mexico, USA

    Bette Korber, Robert Funkhouser, Michael Fugate & James Theiler

  3. The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, 87501, New Mexico, USA

    Bette Korber, Thomas B Kepler, Peter T Hraber & Robert Funkhouser

  4. Duke University Medical Center, Durham, 27708, North Carolina, USA

    Thomas B Kepler

  5. The Feinberg School of Medicine, Northwestern University, 676 North Saint Clair Street, Chicago, 60611, Illinois, USA

    Kevin Kunstman, Samuel Wu, John Phair & Steven Wolinsky

  6. Roche Molecular Systems, 1145 Atlantic Avenue, Alameda, 94501, California, USA

    Henry Erlich

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Correspondence to Steven Wolinsky.

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Trachtenberg, E., Korber, B., Sollars, C. et al. Advantage of rare HLA supertype in HIV disease progression. Nat Med 9, 928–935 (2003). https://doi.org/10.1038/nm893

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