期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 16, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI148979
关键词
-
资金
- NIH [R01-AI102663, R01-AI162168]
The study reveals that HLA-E-restricted CD8(+) T cell responses play a crucial role in determining the immunodominance of CD8(+) T cell responses in HIV infection, shedding light on the immune mechanisms involved in HIV pathogenesis.
CD8(+) T cell responses restricted by MHC-E, a nonclassical MHC molecule, have been associated with protection in an SIV/rhesus macaque model. The biological relevance of HLA-E-restricted CD8(+) T cell responses in HIV infection, however, remains unknown. In this study, CD8(+) T cells responding to HIV-1 Gag peptides presented by HLA-E were analyzed. Using in vitro assays, we observed HLA-E-restricted T cell responses to what we believe to be a newly identified subdominant Gag-KL9 as well as a well-described immunodominant Gag-KF11 epitope in T cell lines derived from chronically HIV-infected patients and also primed from healthy donors. Blocking of the HLA-E/KF11 binding by the B7 signal peptide resulted in decreased CD8(+) T cell responses. KF11 presented via HLA-E in HIV-infected cells was recognized by antigen-specific CD8(+) T cells. Importantly, bulk CD8(+) T cells obtained from HIV-infected individuals recognized infected cells via HLA-E presentation. Ex vivo analyses at the epitope level showed a higher responder frequency of HLA-E-restricted responses to KF11 compared with KL9. Taken together, our findings of HLA-E-restricted HIV-specific immune responses offer intriguing and possibly paradigm-shifting insights into factors that contribute to the immunodominance of CD8(+) T cell responses in HIV infection.
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