Crystallization and preliminary X-ray crystallographic characterization of a public CMV-specific TCR in complex with its cognate antigen

The T‐cell response to human cytomegalovirus is characterized by a dramatic reduction of clonal diversity in patients undergoing chronic inflammation or immunodepression. In order to check whether all the selected high‐avidity T‐cell clones recognize the immunodominant pp65 peptide antigen pp65495–503 (NLVPMVATV) presented by the major histocompatibility complex (MHC) molecule HLA‐A2 in a similar manner, several public high‐affinity T‐cell receptors (TCRs) specific for the pp65495–503–HLA‐A2 complex have been investigated. Expression, purification and crystallization were performed and preliminary crystallographic data were collected to 4.7 Å resolution for the RA15 TCR in complex with the pp65495–503–HLA‐A2 complex. Comparison of the RA15–pp65495–503–HLA‐A2 complex molecular‐replacement solution with the structure of another high‐affinity pp65495–503–HLA‐A2‐specific TCR, RA14, shows a shared docking mode, indicating that the clonal focusing could be accompanied by the selection of a most favoured peptide‐readout mode. However, the position of the RA15 Vβ domain is significantly shifted, suggesting a different interatomic interaction network.