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-Cell …

KD Bourcier, DG Lim, YH Ding, KJ Smith… - Journal of …, 2001 - Am Soc Microbiol
KD Bourcier, DG Lim, YH Ding, KJ Smith, K Wucherpfennig, DA Hafler
Journal of virology, 2001Am Soc Microbiol
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-cell clones was generated by single-cell cloning of
Tax11-19/HLA-A* 0201 tetramer-positive peripheral blood lymphocytes from an HTLV-1-
infected individual. The analyses of TCR usage revealed that the combination of diverse …
Abstract
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-cell clones was generated by single-cell cloning of Tax11-19/HLA-A*0201 tetramer-positive peripheral blood lymphocytes from an HTLV-1-infected individual. 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 beta 13S1 and V alpha 17 chain. We found striking similarities in CDR3 regions of TCR alpha and beta chains between our major group of CD8+ T-cell clones and those originating from different subjects as previously reported, including 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 Tax11-19-reactive T-cell clones expressing V beta 13S1 and V alpha 17 chains. Conserved amino acids in the CDR3 region do not directly contact the Tax11-19 peptide, as corroborated by the crystal structure of B7-TCR, a TCR that is almost identical to VB13S1 clones isolated in this study. Analysis of fine peptide specificity using altered peptide ligands (APL) of Tax11-19 revealed 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 structural framework necessary for the maintenance of the tertiary TCR structure.
American Society for Microbiology