HLA-E–restricted HIV-1–specific CD8+ T cell responses in natural infection |
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Authors: | Anju Bansal Mika N Gehre Kai Qin Sarah Sterrett Ayub Ali Ying Dang Sojan Abraham Margaret C Costanzo Leon A Venegas Jianming Tang N Manjunath Mark A Brockman Otto O Yang June Kan-Mitchell Paul A Goepfert |
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Institution: | 1.Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.;2.Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA.;3.Department of Medicine and AIDS Institute, UCLA, Los Angeles, California, USA.;4.Department of Biomedical Sciences, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, USA.;5.Simon Fraser University, Burnaby, British Columbia, Canada. |
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Abstract: | 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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Keywords: | Infectious disease |
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