Different initiation of pre-TCR and gamma delta TCR signalling

Article

关键词: T-CELL-RECEPTOR;    PROTEIN-TYROSINE KINASE;    ALPHA-BETA;    LINEAGE COMMITMENT;    ANTIGEN RECEPTOR;    LIPID RAFTS;    SH2 DOMAINS;    ACTIVATION;    EXPRESSION;    MEMBRANES;   

DOI  :  10.1038/35020093

来源: SCIE

【 摘 要 】

Lineage choice is of great interest in developmental biology. In the immune system, the alpha beta and gamma delta lineages of T lymphocytes diverge during the course of the beta-, gamma- and delta-chain rearrangement of T-cell receptor (TCR) genes that takes place within the same precursor cell and which results in the formation of the gamma delta TCR or pre-TCR proteins(1-3). The pre-TCR consists of the TCR beta chain covalently linked to the pre-TCR alpha protein, which is present in immature but not in mature T cells which instead express the TCR alpha chain(4,5). Animals deficient in pre-TCR alpha have few alpha beta lineage cells but an increased number of gamma delta T cells. These gamma delta T cells exhibit more extensive TCR beta rearrangement than gamma delta T cells from wild-type mice(6,7). These observations are consistent with the idea that different signals emanating from the gamma delta TCR and pre-TCR instruct lineage commitment(8). Here we show, by using confocal microscopy and biochemistry to analyse the initiation of signalling, that the pre-TCR but not the gamma delta TCR colocalizes with the p56(lck) Src kinase into glycolipid-enriched membrane domains (rafts) apparently without any need for ligation. This results in the phosphorylation of CD3 epsilon and Zap-70 signal transducing molecules. The results indicate clear differences between pre-TCR and gamma delta TCR signalling.

【 授权许可】

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