Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide

作者：Chan Kok Fei; Gully Benjamin S; Gras Stephanie; Beringer Dennis X; Kjer Nielsen Lars; Cebon Jonathan; McCluskey James; Chen Weisan^*; Rossjohn Jamie^*

来源：Nature Communications, 2018, 9(1): 1026.

DOI：10.1038/s41467-018-03321-w

Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (> 10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4(+) TRAJ21(+)-TRBV28(+) TRBJ2-3(+) and TRAV4(+) TRAJ8 (+)-TRBV9(+) TRBJ2-1(+)), originating from a polyclonal T-cell repertoire, bind to HLA-B* 07: 02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-1(60-72). Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-1(60-72)-HLA-B* 07: 02 complex, and induces differing extent of conformational change of the NY-ESO-1(60-72) epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition.

• 出版日期2018-3-12