T-Cell Receptor Repertoire of Lymphocytes Infiltrating Cutaneous Melanoma Is Predominated by Vα Specificities Present in T-Cells of Normal Human Skin

Abstract

Lymphocytes infiltrating solid tumors can be propagated in vitro with interleukin 2 and are then capable, as CD8⁺ cytotoxic T-cells, of specific lysis of autologous tumor targets in a class I-restricted manner. Since the specificity of these cells is determined by their T-cell receptor (TCR) configuration, the aim of this study was to delineate the TCR Vα repertoire of tumor-infiltrating lymphocytes within 24 melanoma specimens and to compare these data with the TCR expression pattern of unaffected peritumoral and normal human skin. While lymphocytes within all skin specimens tested expressed a substantial, albeit limited, heterogeneity of Vα specificities with an average number of 9.0 different Vα gene segments, the Vα repertoire within cutaneous melanoma lesions was significantly more restricted (mean of Vα expression, 3.86; P < 0.001) with a predominance of only 3 Vα families (Vα13, Vα15, and Vα16), all of which were also found to be expressed within normal skin. Collectively, the fact that the TCR Vα repertoire in melanoma is skewed toward the predominance of only a few Vα regions may be indicative of a limited number of melanoma-associated antigenic determinants being involved in the antitumor immune response.