Evidence of the extrathymic development of tyrosinase-related protein-2-recognizing CD8+ T cells with low avidity.
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 beta chain (IL-2Rbeta) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL-2Rbeta+ 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.
Harada
M
M
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. haramamo@med.kurume-u.ac.jp
Yamada
H
H
Tatsugami
K
K
Nomoto
K
K
D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase