Novel Vβ specific germline contacts shape an elite controller T cell response

Wang, Y.; Tsitsiklis, A.; Gao, W.; Chu, H. H.; Zhang, Y.; Li, W.; Wong, W. K.; Deane, C. M.; Neau, D.; Slansky, J.; Thomas, P. G.; Robey, E. A.; Dai, S.

doi:10.1101/2020.05.31.102566

bioRxiv · 10.1101/2020.05.31.102566

Novel Vβ specific germline contacts shape an elite controller T cell response

Wang, Y.·Tsitsiklis, A.·Gao, W.·Chu, H. H.·Zhang, Y.·Li, W.·Wong, W. K.·Deane, C. M.·Neau, D.·Slansky, J.·Thomas, P. G.·Robey, E. A.·Dai, S.

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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 V{beta}2, 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 V{beta}2-containing TCRs and correlates with an unusual V-V{beta} interface, CDR loop conformations, and V{beta}2-specific germline contacts with peptide. V{beta}2 and Ld may represent "specialist" components for antigen recognition that allow for particularly strong and focused T cell responses.

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Wang, Y., Tsitsiklis, A., Gao, W., Chu, H. H., Zhang, Y., Li, W., Wong, W. K., Deane, C. M., Neau, D., Slansky, J., Thomas, P. G., Robey, E. A., Dai, S.. 2020-06-01. Novel Vβ specific germline contacts shape an elite controller T cell response. https://doi.org/10.1101/2020.05.31.102566

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