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

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+ + /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.