表位
抗原
人类白细胞抗原
抗原处理
病毒学
生物
艾滋病疫苗
主要组织相容性复合体
人类免疫缺陷病毒(HIV)
免疫学
MHC I级
疫苗试验
作者
Srona Sengupta,Josephine Zhang,Madison C Reed,Jeanna Yu,Aeryon Kim,Tatiana Boronina,Nathan L Board,James O Wrabl,Kevin Shenderov,Robin A Welsh,Weiming Yang,Andrew E. Timmons,Rebecca Hoh,Robert N. Cole,Steven G. Deeks,Janet D. Siliciano,Robert F. Siliciano,Scheherazade Sadegh-Nasseri
摘要
Distinct CD4+ T cell epitopes have been associated with spontaneous control of HIV-1 replication, but analysis of antigen-dependent factors that influence epitope selection is lacking. To examine these factors, we used a cell-free antigen processing system that incorporates soluble HLA-DR (DR1), HLA-DM (DM), cathepsins, and full-length protein antigens for epitope identification by LC-MS/MS. HIV-1 Gag, Pol, Env, Vif, Tat, Rev, and Nef were examined using this system. We identified 35 novel epitopes, including glycopeptides. Epitopes from smaller HIV-1 proteins mapped to regions of low protein stability and higher solvent accessibility. HIV-1 antigens associated with limited CD4+ T cell responses were processed efficiently, while some protective epitopes were inefficiently processed. 55% of epitopes obtained from cell-free processing induced memory CD4+ T cell responses in HIV-1+ donors, including eight of 19 novel epitopes tested. Thus, an in vitro processing system utilizing the components of Class II processing reveals factors influencing epitope selection of HIV-1 and represents an approach to understanding epitope selection from non–HIV-1 antigens.
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