Nature Medicine
9, 928 - 935 (2003)
Published online: 22 June 2003; | doi:10.1038/nm893
Advantage of rare HLA supertype in HIV disease progressionElizabeth Trachtenberg1, 7, Bette Korber2, 3, 7, Cristina Sollars1, Thomas B Kepler3, 4, Peter T Hraber3, Elizabeth Hayes1, Robert Funkhouser2, 3, Michael Fugate2, James Theiler2, Yen S Hsu1, Kevin Kunstman5, Samuel Wu5, John Phair5, Henry Erlich1, 6
& Steven Wolinsky51
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way Oakland, California 94609, USA. 2
Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. 3
The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, New Mexico 87501, USA. 4
Duke University Medical Center, Durham, North Carolina 27708, USA. 5
The Feinberg School of Medicine, Northwestern University, 676 North Saint Clair Street, Chicago, Illinois 60611, USA. 6
Roche Molecular Systems, 1145 Atlantic Avenue, Alameda, California 94501, USA. 7
These authors contributed equally to this work.
Correspondence should be addressed to Steven Wolinsky swolinsky@northwestern.eduThe 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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