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Journal article
CD8 T cells cross-restricted by HLA-B57 and HLA-E01 recognize HIV Gag with different functional profiles
JCI insight, In Press
2025
PMID: 41411059
Abstract
Few HIV-specific epitopes restricted by non-classical HLA-E have been described, and even less is known about the functional profile of responding CD8 T cells (CD8s). This study evaluates the functional characteristics of CD8s targeting the Gag epitope KF11 (KAFSPEVIPMF) restricted by either HLA-E (E-CD8s) or HLA-B57 (B57-CD8s). CD8s from eight people with HIV (PWH) were cocultured with KF11 peptide presented by cell lines expressing HLA-B*57:01, HLA-E*01:01 or E*01:03. CD8 responses were analyzed using scRNA-seq and scTCR-seq. Supernatants were also assessed for soluble protein profiling. HLA-I multimers were developed to identify CD8s restricted by HLA-B57 and/or HLA-E ex vivo. B57-CD8s secreted higher levels of cytotoxic cytokines such as IFNγ, whereas E-CD8s produced more chemotactic cytokines, including RANTES, CXCL10 (IP-10), and IL27, findings which were corroborated through scRNA sequencing. TCR clonotypes stimulated by KF11 were cross-restricted by HLA-B*57 and HLA-E*01/03 as demonstrated by in vitro T cell reporter assays and ex vivo multimer screening. Ex vivo CD8s were singly restricted by HLA-B57 and HLA-E, with dual restriction only observed in PWH with lower viral load. These findings demonstrate that certain HIV-specific CD8s in PWH exhibit dual restriction by HLA-B*57 and HLA-E*01/03, leading to functionally distinct immune responses depending upon the restricting allele(s).
Details
- Title
- CD8 T cells cross-restricted by HLA-B57 and HLA-E01 recognize HIV Gag with different functional profiles
- Authors/Creators
- Kevin J Maroney - University of Alabama at BirminghamMichael A Rose - University of Alabama at BirminghamAllisa K Oman - University of Alabama at BirminghamAbha Chopra - Murdoch UniversityHua-Shiuan Hsieh - Simon Fraser UniversityZerufael Derza - Simon Fraser UniversityRachel Waterworth - Simon Fraser UniversityMark A Brockman - Simon Fraser UniversitySpyros A Kalams - Vanderbilt University Medical CenterAnju Bansal - University of Alabama at BirminghamPaul A Goepfert - University of Alabama at Birmingham
- Publication Details
- JCI insight, In Press
- Identifiers
- 991005839954007891
- Copyright
- © 2025, Maroney et al.
- Murdoch Affiliation
- Personalised Medicine Centre
- Language
- English
- Resource Type
- Journal article
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