Impact of HLA class I functional divergence on HIV control

Heterozygosity of ( ) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a fu...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2024-01, Vol.383 (6680), p.319-325
Main Authors: Viard, Mathias, O'hUigin, Colm, Yuki, Yuko, Bashirova, Arman A, Collins, David R, Urbach, Jonathan M, Wolinsky, Steven, Buchbinder, Susan, Kirk, Gregory D, Goedert, James J, Michael, Nelson L, Haas, David W, Deeks, Steven G, Walker, Bruce D, Yu, Xu, Carrington, Mary
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Antigens
Disease Progression
Female
Heterozygote
Histocompatibility antigen HLA
HIV
HIV Infections - genetics
HIV Infections - pathology
HLA-B Antigens - genetics
Human immunodeficiency virus
Humans
Immune response
Immune system
Lymphocytes
Lymphocytes T
Male
Middle Aged
Peptides
Peptides - genetics
Peptides - immunology
Young Adult
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Summary:Heterozygosity of ( ) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles. Greater functional divergence for pairs of HLA-A and/or HLA-B allotypes was associated with slower AIDS progression and independently with enhanced viral load control. The metric predicts immune breadth at the peptide level rather than gene level and redefines heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where heterozygote advantage occurs.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.adk0777