Conserved CDR3 regions in T-cell receptor (TCR) CD8(+) T cells that recognize the Tax11-19/HLA-A*0201 complex in a subject infected with human T-Cellleukemia virus type 1: Relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure

We investigated the T-cell receptor (TCR) repertoire of CD8(+) T cells that recognize the Tax11-19 immunodominant epitope of Tax protein expressed by human T-cell leukemia virus (HTLV-1) that is implicated in the disease HTLV -1-associated myelopathy (HAM/TSP). A panel of Tax11-19-reactive CD8(+) T-c ell clones was generated by single-cell cloning of Tax11-19/HLA-A*0201 tetr amer-positive peripheral blood lymphocytes from an HTLV-1-infected individu al. The analyses of TCR usage revealed that the combination of diverse TCR alpha and beta chains could be used for the recognition of Tax11-19 but the major population of T-cell clones (15 of 24 clones) expressed the TCR V be ta 13S1 and V alpha 17 chain. We found striking similarities in CDR3 region s of TCR alpha and beta chains between our major group of CD8(+) T-cell clo nes and those originating from different subjects as previously reported, i ncluding TCRs with resolved crystal structures. A 3-amino-acid sequence (PG -G) in the CDR3 region of the V beta chain was conserved among all the Tax1 1-19-reactive T-cell clones expressing V beta 13S1 and V alpha 17 chains. C onserved amino acids in the CDR3 region do not directly contact the Tax11-1 9 peptide, as corroborated by the crystal structure of B7-TCR, a TCR that i s almost identical to VB13S1 clones isolated in this study. Analysis of fin e peptide specificity using altered peptide ligands (APL) of Tax11-19 revea led a similar recognition pattern among this panel of T-cell clones. These data suggest that the PG-G amino acids in the CDR3 beta loop provide a stru ctural framework necessary for the maintenance of the tertiary TCR structur e.