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[Cancer Research 61, 2047-2054, March 1, 2001]
© 2001 American Association for Cancer Research

Immunology

Melanoma Patients Respond to a Cytotoxic T Lymphocyte-defined Self-Peptide with Diverse and Nonoverlapping T-Cell Receptor Repertoires1

Pierre-Yves Dietrich, Paul R. Walker, Anne-Lise Quiquerez, Gaelle Perrin, Valerie Dutoit, Danielle Liénard, Philippe Guillaume, Jean-Charles Cerottini, Pedro Romero and Danila Valmori2

Division of Oncology, Laboratory of Tumor Immunology, University Hospital, 1211 Geneva 14, Switzerland [P-Y. D., P. R. W., A-L. Q., G. P.], and Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch [D. V., V. D., J-C. C., P. R.], and Multidisciplinary Oncology Center [D. L., P. G.], Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

HLA-A2+ melanoma patients develop naturally a strong CD8+ T cell response to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptide tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymph nodes of two HLA-A2+ melanoma patients and analyzed their TCR ß chain V segment and complementarity determining region 3 length and sequence. We found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR ß chain variable gene segment usage and clonal composition. In addition, immune TCR repertoires selected in the patients were not overlapping. In contrast to previously characterized CD8+ T-cell responses to viral infections, this study provides evidence against usage of highly restricted TCR repertoire in the natural response to a self-differentiation tumor antigen.




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Copyright © 2001 by the American Association for Cancer Research.