INTRATHYMIC SELECTION OF NK1.1(+)ALPHA BETA 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(+)alpha/beta T cell recepto r (TCR)(+) thymocytes were analyzed using TCR-transgenic (B10,D2 x DO1 0)F-1 and (C57BL/6 x DO10)F-1 mice and Rag-1(-/-)/DO10 mice, which had been established by breeding and backcrossing between Rag-l(-/-)and D O10 mice. Almost all T cells from these mice were shown to bear V alph a 13/V beta 8.2 that is specific for chicken ovalbumin (cOVA) and rest ricted to I-A(d). A normal proportion of the NK1.1(+) V alpha 13/V bet a 8.2(+) thymocytes was generated in these mice. However, the actual c ell 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 proportio ns of NK1.1(+) V alpha 13/V beta 8.2(+) cells were detected in the spl eens from I-A(d/d) and I-A(b/d) mice. It was shown that the splenic NK 1.1(+) T cells of the I-A(b/d) mice were anergized against stimulation through TCR, When (B10.D2 x DO10)F-1 and (C57BL/6 x DO10)F-1 mice wer e given cOVA, extensive or intermediate elimination of NK1.1(+)alpha/b eta TCR+ thymocytes was induced in I-A(d/d) or I-A(b/d) mice, respecti vely. However, the clonal elimination was not as complete as that seen in the major NK1.1(-) thymocyte population. The present findings indi cate that normal generation of NK1.1(+)alpha/beta TCR+ thymocytes occu rs in the absence of V alpha 14-J alpha 281 and that substantial negat ive selection operates on the NK1.1(+)alpha/beta TCR+ cells.