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

Galperin M, Farenc C, Mukhopadhyay M, Jayasinghe D, Decroos A, Benati D, Tan LL, Ciacchi L, Reid HH, Rossjohn J, Chakrabarti LA, Gras S
Sci Immunol 3 (2018)
Related entries: 6cph, 6cpl, 6cpn, 6cpo, 6cqj, 6cql, 6cqn, 6cqq

Cited: 33 times
EuropePMC logo PMID: 29884618

Abstract

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.

Reviews - 6cqr mentioned but not cited (1)

  1. The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics. Chatzileontiadou DSM, Sloane H, Nguyen AT, Gras S, Grant EJ. Int J Mol Sci 22 E73 (2020)

Articles - 6cqr mentioned but not cited (3)

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  1. T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Shepherd FR, McLaren JE. Int J Mol Sci 21 E6144 (2020)
  2. Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions. Kervevan J, Chakrabarti LA. Int J Mol Sci 22 E523 (2021)
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  3. Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses. Brentville VA, Metheringham RL, Daniels I, Atabani S, Symonds P, Cook KW, Vankemmelbeke M, Choudhury R, Vaghela P, Gijon M, Meiners G, Krebber WJ, Melief CJM, Durrant LG. J Immunother Cancer 8 e000560 (2020)
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