학술논문
A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design
Document Type
article
Author
Sengupta, Srona; Zhang, Josephine; Reed, Madison C; Yu, Jeanna; Kim, Aeryon; Boronina, Tatiana N; Board, Nathan L; Wrabl, James O; Shenderov, Kevin; Welsh, Robin A; Yang, Weiming; Timmons, Andrew E; Hoh, Rebecca; Cole, Robert N; Deeks, Steven G; Siliciano, Janet D; Siliciano, Robert F; Sadegh-Nasseri, Scheherazade
Source
Journal of Experimental Medicine. 220(7)
Subject
Language
Abstract
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.