HLA-E-restricted HIV-1-specific [CD8.sup.+] T cell responses in natural infection

• Published in: The Journal of clinical investigation 2021-08, Vol.131 (16)
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: CD8 lymphocytes; Development and progression; Health aspects; Histocompatibility antigens; HIV infection; HLA histocompatibility antigens; Immune response
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI148979

[CD8.sup.+] 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.sup.+] T cell responses in HIV infection, however, remains unknown. In this study, [CD8.sup.+] 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.sup.+] T cell responses. KF11 presented via HLA-E in HIV-infected cells was recognized by antigen-specific [CD8.sup.+] T cells. Importantly, bulk [CD8.sup.+] 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.sup.+] T cell responses in HIV infection.