Peptide Centric Vβ Specific Germline Contacts Shape a Specialist T Cell Response.

Publication Type:

Journal Article


Front Immunol, Volume 13, p.847092 (2022)


CD8-Positive T-Lymphocytes, Germ Cells, Humans, Molecular Conformation, Peptides, Receptors, Antigen, T-Cell


<p>Certain CD8 T cell responses are particularly effective at controlling infection, as exemplified by elite control of HIV in individuals harboring HLA-B57. To understand the structural features that contribute to CD8 T cell elite control, we focused on a strongly protective CD8 T cell response directed against a parasite-derived peptide (HF10) presented by an atypical MHC-I molecule, H-2Ld. This response exhibits a focused TCR repertoire dominated by Vβ2, and a representative TCR (TG6) in complex with Ld-HF10 reveals an unusual structure in which both MHC and TCR contribute extensively to peptide specificity, along with a parallel footprint of TCR on its pMHC ligand. The parallel footprint is a common feature of Vβ2-containing TCRs and correlates with an unusual Vα-Vβ interface, CDR loop conformations, and Vβ2-specific germline contacts with peptides. Vβ2 and Ld may represent &quot;specialist&quot; components for antigen recognition that allows for particularly strong and focused T cell responses.</p>

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