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Journal of Virology, October 2001, p. 9836-9843, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9836-9843.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Katarzyna D. Bourcier,1,* Dong-Gyun Lim,1 Yuan-Hua Ding,2,dagger Kathrine J. Smith,2,Dagger Kai Wucherpfennig,3 and David A. Hafler1

Laboratory of Molecular Immunology, Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School,1 Department of Molecular and Cellular Biology, Harvard University,2 and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,3 Boston, Massachusetts 02115

Received 18 May 2001/Accepted 6 July 2001

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.

* Corresponding author. Mailing address: Laboratory of Molecular Immunology, Center for Neurological Disorders, Brigham and Women's Hospital, 77 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 525-5346. Fax: (617) 525-5333. E-mail: kbourcier{at}rics.bwh.harvard.edu.

dagger Present address: Pfizer Inc., Cambridge, MA 02139.

Dagger Present address: SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom.

Journal of Virology, October 2001, p. 9836-9843, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9836-9843.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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