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 language | English (US) |
|---|---|
| Pages (from-to) | 928-935 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 9 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2003 |
Funding
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.).
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
