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TY - JOUR AU - Fischer, Klaus-Dieter AU - Zmuidzinas, Antanina AU - Gardner, Sandra AU - Barbacid, Mariano AU - Bernstein, Alan AU - Guidos, Cynthia PY - 1995 DA - 1995/03/01 TI - Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+CDS+thymocytes JO - Nature SP - 474 EP - 476 VL - 374 IS - 6521 AB - DURING lymphocyte development, cellular proliferation and posi-tive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors1,2. These processes are initiated when engage-ment of growth-factor receptors, or the T3,4 and B5 lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav3,6,7. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lympho-cytes in the RAG-2 blastocyst complementation assay8. Further-inore, Vav-deficient T lymphocytes showed severely unpaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/ CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4 + CD8 + precursors into mature CD4 + CD8- or CD4-CD8+ T cells. SN - 1476-4687 UR - https://doi.org/10.1038/374474a0 DO - 10.1038/374474a0 ID - Fischer1995 ER -