Public T cell clonotypes are selected in HLA-B∗57:01+/HIV+ patients independently of the viral load

Demetra S.M. Chatzileontiadou; Christian A. Lobos; Hayden Robson; Coral-Ann Almedia; Christopher Szeto; Alison Castley; Lloyd J. D’Orsogna; Stephanie Gras

Cell Reports (Aug 2024)

Public T cell clonotypes are selected in HLA-B∗57:01+/HIV+ patients independently of the viral load

Demetra S.M. Chatzileontiadou,
Christian A. Lobos,
Hayden Robson,
Coral-Ann Almedia,
Christopher Szeto,
Alison Castley,
Lloyd J. D’Orsogna,
Stephanie Gras

Affiliations

Demetra S.M. Chatzileontiadou: Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Corresponding author
Christian A. Lobos: Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Hayden Robson: Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Coral-Ann Almedia: School of Medicine, University of Western Australia, Nedlands, WA 6009, Australia
Christopher Szeto: Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Alison Castley: Department of Clinical Immunology and PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
Lloyd J. D’Orsogna: School of Medicine, University of Western Australia, Nedlands, WA 6009, Australia; Department of Clinical Immunology and PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
Stephanie Gras: Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Corresponding author

Journal volume & issue: Vol. 43, no. 8
p. 114555

Abstract

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Summary: HIV controllers can control viral replication and remain healthy, but the mechanism behind this control is unknown. Despite human leukocyte antigen (HLA) diversity in the population, almost 50% of HIV controllers express the HLA-B∗57:01 molecule, which presents, among others, the Gag-derived epitope TW10. Given TW10’s presentation in early infection, TW10-specific T cells could participate in the control of HIV. Here, we study the strength and functionality of TW10-specific T cells from HLA-B∗57:01+/HIV+ controller and non-controller individuals. We determine the TW10-specific T cell receptor (TCR) repertoire, revealing a bias in TCR gene usage with the presence of a public TCR. We determine that the T cell response is polyfunctional regardless of the viral load, despite the low affinity of TW10-specific TCRs. We solve the crystal structure of HLA-B∗57:01-TW10 in complex with a TCR, providing the basis of recognition that underpins the strong TRBV5 bias observed in TW10-specific clonotypes.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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