Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection

Cai C, Keoshkerian E, Wing K, Samir J, Effenberger M, Schober K, Bull RA, Lloyd AR, Busch DH, Luciani F (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Immunology and Cell Biology Nature Publishing Group: Open Access Hybrid Model Option A

DOI: 10.1111/imcb.12791

Abstract

CD8+ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide–major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T-cell population with specificity for a hepatitis C virus (HCV)–derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and koff = 5.73 × 10−4) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR–pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.

Authors with CRIS profile

Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

University of New South Wales (UNSW) AU Australia (AU) Kirby Institute AU Australia (AU) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Cai, C., Keoshkerian, E., Wing, K., Samir, J., Effenberger, M., Schober, K.,... Luciani, F. (2024). Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection. Immunology and Cell Biology. https://doi.org/10.1111/imcb.12791

MLA:

Cai, Curtis, et al. "Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection." Immunology and Cell Biology (2024).

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