AUTHOR=Wang Yang , Tsitsiklis Alexandra , Devoe Stephanie , Gao Wei , Chu H. Hamlet , Zhang Yan , Li Wei , Wong Wing Ki , Deane Charlotte M. , Neau David , Slansky Jill E. , Thomas Paul G. , Robey Ellen A. , Dai Shaodong TITLE=Peptide Centric Vβ Specific Germline Contacts Shape a Specialist T Cell Response JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.847092 DOI=10.3389/fimmu.2022.847092 ISSN=1664-3224 ABSTRACT=

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 “specialist” components for antigen recognition that allows for particularly strong and focused T cell responses.