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Intracytoplasmic Tail in Double Negative to Double Positive Thymocyte Differentiation 1
,
* Lymphocyte Development Laboratory, Institut de Recherches Cliniques de Montreal (I.R.C.M.), Montreal, Quebec, Canada;
Department of Microbiology and Immunology, McGill University;
Division of Experimental Division, McGill University; and
Department of Medicine, University of Montreal, Montreal, Quebec, Canada
The preTCR is associated with signal-transducing CD3
, 
, 
, and 
polypeptides. It is generally agreed that CD3 chains play redundant roles in the receptor-mediated signal transduction. In the present study, we show that the intracytoplasmic (IC) domain of CD3 is essential for early thymocyte maturation. We demonstrate that the IC domain-deleted CD3 fails to restore the double negative (DN) to double positive (DP) thymocyte development in CD3-deficient mice. Additional experiments show that the membrane proximal basic amino acid rich sequence in the IC domain of CD3 is sufficient for the DN to DP differentiation, whereas the proline rich sequence is required for efficient proliferation. This is probably due to impaired ligand independent recruitment of Nck to the proline rich sequence motif of CD3 within the context of the preTCR. The data presented in this study elucidates mechanistic basis for the preTCR-induced proliferation of the DN thymocytes and have identified distinct roles for individual motifs of CD3 in the preTCR-mediated differentiation and proliferation. These data provide the first genetic and phenotypic evidence for requirement of the IC domain of a CD3 chain in thymocyte development.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the C.I.H.R. operating Grant MOP81145.
2 Address correspondence and reprint requests to Dr. Vibhuti P. Dave, Lymphocyte Development Laboratory, 110 Pine Avenue West, I.R.C.M., Montreal, Quebec, Canada. E-mail address: vibhuti.dave{at}ircm.qc.ca
3 Abbreviations used in this paper: DN, double negative; DP, double positive; SP, single positive; ER, endoplasmic reticulum; WT, wild type; CIC, CD3 and CD3 complex; PRS, proline rich sequence; IC, intracytoplasmic; LN, lymph node; RP16, ribosomal protein 16; BRS, basic amino acid rich sequence. 7-AAD, 7-aminoactinomycin D; Q-PCR, quantitative PCR.
4 The online version of this article contains supplemental material.
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