近日，美国国立癌症研究所Mary Carrington及其课题组揭示HLA I类的功能分化对艾滋病毒控制的影响。相关论文于2024年1月19日发表在《科学》杂志上。

研究人员表示，人类白细胞抗原（HLA）Ⅰ类基因的杂合性与艾滋病病毒感染后的有益结果有关，这可能是由于艾滋病病毒表位呈递和细胞毒性T细胞反应的广度更大。然而，不同的异型配对在结合共享肽集的程度上存在差异。

研究人员开发了一种功能差异度量方法，用于测量异型相关肽结合谱的成对互补性。HLA-A和/或HLA-B异型配对的功能差异越大，艾滋病进展越慢，病毒载量控制能力越强。该指标从肽水平而非基因水平预测免疫广度，并将HLA杂合性重新定义为一个连续体，可对疾病预后产生不同影响。功能差异可能会影响对其他感染、疫苗接种、免疫疗法和其他具有HLA杂合性优势的疾病的反应。

附：英文原文

Title: Impact of HLA class I functional divergence on HIV control

Author: Mathias Viard, Colm O’hUigin, Yuko Yuki, Arman A. Bashirova, David R. Collins, Jonathan M. Urbach, Steven Wolinsky, Susan Buchbinder, Gregory D. Kirk, James J. Goedert, Nelson L. Michael, David W. Haas, Steven G. Deeks, Bruce D. Walker, Xu Yu, Mary Carrington

Issue&Volume: 2024-01-19

Abstract: 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.

DOI: adk0777

Source: https://www.science.org/doi/10.1126/science.adk0777