Author:
Joglekar Alok V.,Liu Zhe,Weber Jeffrey K.,Ouyang Yong,Jeppson John D.,Noh Won Jun,Lamothe-Molina Pedro A.,Chen Huabiao,Kang Seung-gu,Bethune Michael T.,Zhou Ruhong,Walker Bruce D.,Baltimore David
Abstract
HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties. Transduced T cells comparably, albeit modestly, also suppressed HIV infection in vitro and in humanized mice. We also performed extensive molecular dynamics simulations that provided a structural basis for similarities in cytotoxicity and epitope cross-reactivity. These results demonstrate that the differential abilities of HIV-specific CD8+ T cells from HCs and CPs are not genetically encoded in the TCRs alone and must depend on additional factors.
Publisher
Proceedings of the National Academy of Sciences
Cited by
13 articles.
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