Impact of HLA class I functional divergence on HIV control

• 成果类型: Article
• 署名作者: 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
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University; Northwestern University; Feinberg School of Medicine; San Francisco Department of Public Health; University of California System; University of California San Francisco; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Walter Reed Army Institute of Research (WRAIR); United States Department of Defense; United States Army; Vanderbilt University; University of California System; University of California San Francisco; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11851
• DOI: 10.1126/science.adk0777
• 发表日期: 2024-01-19
• 页码: 319-325
• 关键词: antigen presentation; tapasin; homozygosity; polymorphism

摘要

Heterozygosity of Human leukocyte antigen (HLA) 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 HLA heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where HLA heterozygote advantage occurs.