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-A(d)

Generation and negative selection of NK1.1(+)α/β T cell receptor (TCR)(+) thymocytes were analyzed using TCR-transgenic (B10.D2 × DO10)F(1) and (C57BL/6 × DO10)F(1) mice 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 Vα13/Vβ8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-A(d). A normal proportion of the NK1.1(+) Vα13/Vβ8.2(+) thymocytes was generated in these mice. However, the actual cell number of both NK1.1(+) and NK1.1(−) thymocytes in I-A(d/d) mice (positive selecting background) was larger than that in I-A(b/d) mice (negative selecting background). Markedly low but significant proportions of NK1.1(+) Vα13/Vβ8.2(+) cells were detected in the spleens from I-A(d/d) and I-A(b/d) mice. It was shown that the splenic NK1.1(+) T cells of the I-A(b/d) mice were anergized against stimulation through TCR. When (B10.D2 × DO10)F(1) and (C57BL/6 × DO10)F(1) mice were given cOVA, extensive or intermediate elimination of NK1.1(+)α/βTCR(+) thymocytes was induced in I-A(d/d) or I-A(b/d) mice, 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/βTCR(+) thymocytes occurs in the absence of Vα14-Jα281 and that substantial negative selection operates on the NK1.1(+)α/βTCR(+) cells.