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Distinct Sets of αβ TCRs Confer Similar Recognition of Tumor Antigen NY-ESO-1₁₅₇₋₁₆₅ by Interacting with Its Central Met/Trp Residues
Laurent Derré, Marc Bruyninx, Petra Baumgaertner, Mathias Ferber, Daphné Schmid, Antoine Leimgruber, Vincent Zoete, Pedro Romero, Olivier Michielin, Daniel E. Speiser and Nathalie Rufer
Proceedings of the National Academy of Sciences of the United States of America
Vol. 105, No. 39 (Sep. 30, 2008), pp. 15010-15015
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25464352
Page Count: 6
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Naturally acquired immune responses against human cancers often include CD8⁺ T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1₁₅₇₋₁₆₅-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with α-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1₁₅₇₋₁₆₅ peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of αβ TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.
Proceedings of the National Academy of Sciences of the United States of America © 2008 National Academy of Sciences