T-CELL RECEPTOR REPERTOIRE OF LYMPHOCYTES INFILTRATING CUTANEOUS MELANOMA IS PREDOMINATED BY V-ALPHA SPECIFICITIES PRESENT IN T-CELLS OF NORMAL HUMAN SKIN

Lymphocytes infiltrating solid tumors can be propagated in vitro with interleukin 2 and are then capable, as CD8(+) cytotoxic T-cells, of sp ecific lysis of autologous tumor targets in a class I-restricted manne r. Since the specificity of these cells is determined by their T-cell receptor (TCR) configuration, the aim of this study was to delineate t he TCR V alpha repertoire of tumor-infiltrating lymphocytes within 24 melanoma specimens and to compare these data with the TCR expression p attern of unaffected peritumoral and normal human skin. While lymphocy tes within all skin specimens tested expressed a substantial, albeit l imited, heterogeneity of V alpha specificities with an average number of 9.0 different V alpha gene segments, the V alpha repertoire within cutaneous melanoma lesions was significantly more restricted (mean of V alpha expression, 3.86; P < 0.001) with a predominance of only 3 V a lpha families (V alpha 13, V alpha 15, and V alpha 16), all of which w ere also found to be expressed within normal skin. Collectively, the f act that the TCR V alpha repertoire in melanoma is skewed toward the p redominance of only a few V alpha regions may be indicative of a limit ed number of melanoma-associated antigenic determinants being involved in the antitumor immune response.