Intrathymic Selection of NK1.1+α /β T Cell Antigen Receptor (TCR)+Cells in Transgenic Mice Bearing TCR Specific for Chicken Ovalbumin and Restricted to I-Ad

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-07, Vol.95 (14), p.8199-8204
• Main Authors: Iwabuchi, Chikako, Iwabuchi, Kazuya, Nakagawa, Ken-Ichi, Takayanagi, Toshiaki, Nishihori, Hiroki, Tone, Saori, Ogasawara, Kazumasa, Good, Robert A., Onoe, Kazunori
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Biological Sciences; Cell Differentiation - immunology; Cell lines; Cellular biology; Chickens; Genetic engineering; Histocompatibility Antigens Class II - immunology; Immunology; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Mice; Mice, Transgenic; Monoclonal antibodies; Negative selection; Ovalbumin - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Rodents; Spleen; Spleen cells; T cell antigen receptors; T lymphocytes; Thymocytes; Thymus Gland - immunology; Thymus Gland - pathology; Transgenic animals
• ISSN: 0027-8424; 1091-6490

Generation and negative selection of NK1.1+α /β T cell receptor (TCR)+thymocytes were analyzed using TCR-transgenic (B10.D2 × DO10)F1and (C57BL/6 × DO10)F1mice and Rag-1-/-/DO10 mice, which had been established by breeding and backcrossing between Rag-1-/-and DO10 mice. Almost all T cells from these mice were shown to bear Vα 13/Vβ 8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1+Vα 13/Vβ 8.2+thymocytes was generated in these mice. However, the actual cell number of both NK1.1+and NK1.1-thymocytes in I-Ad/dmice (positive selecting background) was larger than that in I-Ab/dmice (negative selecting background). Markedly low but significant proportions of NK1.1+Vα 13/Vβ 8.2+cells were detected in the spleens from I-Ad/dand I-Ab/dmice. It was shown that the splenic NK1.1+T cells of the I-Ab/dmice were anergized against stimulation through TCR. When (B10.D2 × DO10)F1and (C57BL/6 × DO10)F1mice were given cOVA, extensive or intermediate elimination of NK1.1+α /β TCR+thymocytes was induced in I-Ad/dor I-Ab/dmice, respectively. However, the clonal elimination was not as complete as that seen in the major NK1.1-thymocyte population. The present findings indicate that normal generation of NK1.1+α /β TCR+thymocytes occurs in the absence of Vα 14-Jα 281 and that substantial negative selection operates on the NK1.1+α /β TCR+cells.