6CPO

Crystal structure of DR15 presenting the RQ13 peptide

Summary for 6CPO

• Entry DOI: 10.2210/pdb6cpo/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA-DRB1 protein, RQ13, ... (7 entities in total)
• Functional Keywords: immune receptor, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 90945.61

Authors

Farenc, C.,Gras, S.,Rossjohn, J. (deposition date: 2018-03-13, release date: 2018-06-06, Last modification date: 2024-11-06)

Primary citation

Galperin, M.,Farenc, C.,Mukhopadhyay, M.,Jayasinghe, D.,Decroos, A.,Benati, D.,Tan, L.L.,Ciacchi, L.,Reid, H.H.,Rossjohn, J.,Chakrabarti, L.A.,Gras, S.
CD4+T cell-mediated HLA class II cross-restriction in HIV controllers.
Sci Immunol, 3:-, 2018

PubMed 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.

PubMed: 29884618
DOI: 10.1126/sciimmunol.aat0687

Experimental method

X-RAY DIFFRACTION (2.4 Å)