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Evidence of the extrathymic development of tyrosinase‐related protein‐2‐recognizing CD8 + T cells with low avidity
Author(s) -
Harada, Mamoru,
Yamada Hisakata,
Tatsugami Katsunori,
Nomoto Kikuo
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01278.x
Subject(s) - avidity , cd8 , cytotoxic t cell , tyrosinase , immunology , biology , chemistry , biochemistry , antigen , enzyme , in vitro
Summary The majority of the human tumour‐associated antigens characterized to date are derived from non–mutated self‐proteins. However, nothing is known about the development of autoreactive and tumour‐associated antigen‐recognizing T cells. Tyrosinase‐related protein (TRP)‐2 is a non‐mutated melanocyte differentiation antigen and TRP‐2‐recognizing CD8 + T cells are known to show responses to melanoma both in humans and mice. In addition, TRP‐2‐reactive T cells with low avidity have been suggested to be readily induced from the spleen cells of naïve mice. On the other hand, recent reports suggest that self antigen‐reactive CD8 + T cells can be positively selected in the periphery. In this study, we tested the possibility that TRP‐2‐reactive CD8 + T cells in naïve mice could develop via the extrathymic pathway. As a consequence, TRP‐2‐reactive CD8 + T cell precursors in naïve C57BL/6 mice were suggested to express both interleukin‐2 (IL‐2) receptor β chain (IL‐2Rβ) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL‐2Rβ + CD44 + CD8 + T cells were detected in the adult thymectomized and bone marrow‐reconstituted mice, and functional TRP‐2‐reactive T cells were generated from their spleen cells. Overall, these results suggest that low avidity CD8 + T cells recognizing TRP‐2 can be developed extrathymically.