- Wang, Yang;
- Tsitsiklis, Alexandra;
- Devoe, Stephanie;
- Gao, Wei;
- Chu, H;
- Zhang, Yan;
- Li, Wei;
- Wong, Wing;
- Deane, Charlotte;
- Neau, David;
- Slansky, Jill;
- Thomas, Paul;
- Robey, Ellen;
- Dai, Shaodong
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.