Melanoma patients respond to a cytotoxic T lymphocyte-defined self-peptidewith diverse and nonoverlapping T-cell receptor repertoires

HLA-A2(+) melanoma patients develop naturally a strong CD8(+) T cell respon se to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptid e tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymp h nodes of two HLA-A2(+) melanoma patients and analyzed their TCR beta chai n V segment and complementarity determining region 3 length and sequence. W e found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR beta chain variable gene segment usage and clonal composition, in addition, immune TCR repertoires selected in the pa tients 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 sel f-differentiation tumor antigen.