CD4 + T cell–mediated HLA class II cross-restriction in HIV controllers

Moran Galperin (1) , Carine Farenc (2) , Madhura Mukhopadhyay (1) , Dhilshan Jayasinghe (2) , Amandine Decroos (1) , Daniela Benati (1) , Li Lynn Tan (2) , Lisa Ciacchi (2) , Hugh H Reid (2) , Jamie Rossjohn (2, 3) , Lisa A. Chakrabarti (1) , Stéphanie Gras (2)

1 Pathogénie Virale - Viral Pathogenesis
2 Monash University [Clayton]
3 Cardiff University

Rare individuals, termed HIV controllers, spontaneously control HIV infection by mounting efficient T cell responses against the virus. Protective CD4+ T cell responses from HIV controllers involve high-affinity public T cell receptors (TCRs) recognizing an immunodominant capsid epitope (Gag293) presented by a remarkably broad array of human leukocyte antigen (HLA) class II molecules. Here, we determine the structures of a prototypical public TCR bound to HLA-DR1, HLA-DR11, and HLA-DR15 molecules presenting the Gag293 epitope. TCR recognition was driven by contacts with the Gag293 epitope, a feature that underpinned the extensive HLA cross-restriction. These high-affinity TCRs promoted mature immunological synapse formation and cytotoxic capacity in both CD4+ and CD8+ T cells. The public TCRs suppressed HIV replication in multiple genetic backgrounds ex vivo, emphasizing the functional advantage conferred by broad HLA class II cross-restriction.

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Microbiology and Parasitology

Moran Galperin, Carine Farenc, Madhura Mukhopadhyay, Dhilshan Jayasinghe, Amandine Decroos, et al.. CD4 + T cell–mediated HLA class II cross-restriction in HIV controllers. Science Immunology, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩. ⟨pasteur-02132543⟩