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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: 6cpl, 6cpn, 6cpo, 6cqj, 6cql, 6cqn, 6cqq, 6cqr

Cited: 34 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.

Articles - 6cph mentioned but not cited (1)

  1. Impact of HLA-DR Antigen Binding Cleft Rigidity on T Cell Recognition. Szeto C, Bloom JI, Sloane H, Lobos CA, Fodor J, Jayasinghe D, Chatzileontiadou DSM, Grant EJ, Buckle AM, Gras S. Int J Mol Sci 21 E7081 (2020)


Reviews citing this publication (8)

  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)
  2. T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Shepherd FR, McLaren JE. Int J Mol Sci 21 E6144 (2020)
  3. 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)
  4. The role of T-cell immunity in COVID-19 severity amongst people living with type II diabetes. Tong ZWM, Grant E, Gras S, Wu M, Smith C, Barrett HL, Gallo LA, Short KR. FEBS J 288 5042-5054 (2021)
  5. Immune Literacy: Reading, Writing, and Editing Adaptive Immunity. Csepregi L, Ehling RA, Wagner B, Reddy ST. iScience 23 101519 (2020)
  6. Understanding the CD8 T-cell response in natural HIV control. Boppana S, Goepfert P. F1000Res 7 F1000 Faculty Rev-985 (2018)
  7. Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products. Santacroce L, Topi S, Charitos IA, Lovero R, Luperto P, Palmirotta R, Jirillo E. Pathophysiology 31 18-31 (2024)
  8. Protective HLA-B57: T cell and natural killer cell recognition in HIV infection. Lobos CA, Downing J, D'Orsogna LJ, Chatzileontiadou DSM, Gras S. Biochem Soc Trans 50 1329-1339 (2022)

Articles citing this publication (25)



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