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

doi:10.1016/j.celrep.2024.114555

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

Cell Rep. 2024 Aug 27;43(8):114555. doi: 10.1016/j.celrep.2024.114555. Epub 2024 Jul 30.

Authors

Demetra S M Chatzileontiadou¹, Christian A Lobos², Hayden Robson³, Coral-Ann Almedia⁴, Christopher Szeto⁵, Alison Castley⁶, Lloyd J D'Orsogna⁷, Stephanie Gras⁸

Affiliations

¹ 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. Electronic address: d.chatzileontiadou@latrobe.edu.au.
² 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.
³ 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.
⁴ School of Medicine, University of Western Australia, Nedlands, WA 6009, Australia.
⁵ 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.
⁶ Department of Clinical Immunology and PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.
⁷ School of Medicine, University of Western Australia, Nedlands, WA 6009, Australia; Department of Clinical Immunology and PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.
⁸ 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. Electronic address: s.gras@latrobe.edu.au.

PMID: 39083376
DOI: 10.1016/j.celrep.2024.114555

Abstract

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.

Keywords: CP: Immunology; HIV; HIV controller; HLA-B∗57:01; T cell receptor recognition; T cells; TW10 epitope; crystal structure.

MeSH terms

Clone Cells
HIV Infections* / immunology
HIV Infections* / virology
HIV-1 / immunology
HLA-B Antigens* / immunology
HLA-B Antigens* / metabolism
Humans
Male
Receptors, Antigen, T-Cell / immunology
Receptors, Antigen, T-Cell / metabolism
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Viral Load*

Substances

HLA-B Antigens
Receptors, Antigen, T-Cell
HLA-B*57:01 antigen