HLA-E-restricted HIV-1-specific CD8+ T cell responses in natural infection
| Autor: | Bansal, Anju, Gehre, Mika N, Qin, Kai, Sterrett, Sarah, Ali, Ayub, Dang, Ying, Abraham, Sojan, Costanzo, Margaret C, Venegas, Leon A, Tang, Jianming, Manjunath, N, Brockman, Mark A, Yang, Otto O, Kan-Mitchell, June, Goepfert, Paul A |
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| Rok vydání: | 2021 |
| Předmět: |
Immunology
T cells HIV Infections CD8-Positive T-Lymphocytes In Vitro Techniques Medical and Health Sciences Cell Line Vaccine Related Clinical Research HIV Seronegativity Receptors Humans 2.1 Biological and endogenous factors Amino Acid Sequence Vaccine Related (AIDS) gag Gene Products alpha-beta Antigen Presentation Infectious disease Immunodominant Epitopes Prevention Histocompatibility Antigens Class I T-Cell Infectious Diseases HLA-B Antigens Antigen HIV-1 HIV/AIDS Immunization Infection Human Immunodeficiency Virus |
| Zdroj: | The Journal of clinical investigation, vol 131, iss 16 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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