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
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.
