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 leukemia virus type 1: relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure.

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.

• Authors: K D Bourcier, D G Lim, Y H Ding, K J Smith, K Wucherpfennig, D A Hafler
• Journal: Journal of virology (J Virol) Vol. 75 Issue 20 Pg. 9836-43 (Oct 2001) ISSN: 0022-538X [Print] United States
• PMID: 11559817 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Complementarity Determining Regions
• Gene Products, tax
• HLA-A Antigens
• Ligands
• Receptors, Antigen, T-Cell
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Amino Acid Sequence
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Clone Cells
• Complementarity Determining Regions (chemistry, immunology)
• Gene Products, tax (immunology)
• HLA-A Antigens (immunology, metabolism)
• HTLV-I Infections (immunology)
• Human T-lymphotropic virus 1 (immunology)
• Humans
• Ligands
• Molecular Sequence Data
• Receptors, Antigen, T-Cell (chemistry, immunology, metabolism)
• Receptors, Antigen, T-Cell, alpha-beta (genetics)
• Sequence Alignment