| First Author | Baur N | Year | 2001 |
| Journal | Int Immunol | Volume | 13 |
| Issue | 8 | Pages | 1031-42 |
| PubMed ID | 11470773 | Mgi Jnum | J:71151 |
| Mgi Id | MGI:2149240 | Doi | 10.1093/intimm/13.8.1031 |
| Citation | Baur N, et al. (2001) Expression and selection of productively rearranged TCRbeta VDJ genes are sequentially regulated by CD3 signaling in the development of NK1.1(+) alphabeta T cells. Int Immunol 13(8):1031-42 |
| abstractText | The generation of thymic NK1.1(+)alphabetaT (NKT) cells involves positive selection of cells enriched for V(alpha)14/V(beta)8 TCR by CD1d MHC class I molecules. However, it has not been determined whether positive selection is preceded by pre-TCR-dependent beta selection. Here we studied NKT cell development in CD3 signaling-deficient mice (CD3zeta/eta(-/-) and/or p56(lck-/-)) and TCRalpha-deficient mice. In contrast to wild-type mice, NK1.1(+) thymocytes in CD3 signaling-deficient mice are approximately 10-fold reduced in number, do not exhibit V(alpha)14-J(alpha)281 rearrangements and fail to express alphabetaTCR at the cell surface. However, they exhibit TCRbeta VDJ rearrangements and pre-Talpha mRNA, suggesting that they contain pre-NKT cells. Strikingly, pre-NKT cells of CD3zeta/Lck double-deficient mice fail to express TCRbeta mRNA and protein. Whereas in wild-type NKT cells TCRbeta VDJ junctions are selected for productive V(beta)8 and against productive V(beta)5 rearrangements, V(beta)8 and V(beta)5 rearrangements are non-selected in pre-NKT cells of CD3 signaling-deficient mice. Thus, pre-NKT cell development in CD3 signaling-deficient mice is blocked after rearrangement of TCRbeta VDJ genes but before expression of TCRbeta proteins. Most NKT cells of TCRalpha-deficient mice exhibit cell surface gammadeltaTCR. In contrast to pre-NKT cells of CD3 signaling-deficient mice, approximately 25% of NKT cells of TCRalpha-deficient mice exhibit intracellular TCRbeta polypeptide chains. Moreover, both V(beta)8 and V(beta)5 families are selected for in-frame VDJ joints in the TCRbeta(+) NKT cell subset of TCRalpha-deficient mice. The data suggest that CD3 signals regulate initial TCRbeta VDJ gene expression prior to beta selection in developing pre-NKT cells. |
