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 2024 Aug 27

filter terms:

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. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Demetra S M Chatzileontiadou, Christian A Lobos, Hayden Robson, Coral-Ann Almedia, Christopher Szeto, Alison Castley, Lloyd J D'Orsogna, Stephanie Gras. Public T cell clonotypes are selected in HLA-B∗57:01+/HIV+ patients independently of the viral load. Cell reports. 2024 Aug 27;43(8):114555