Different initiation of pre-TCR and gamma delta TCR signalling

Lineage choice is of great interest in developmental biology. In the immune system, the alpha beta and gamma delta lineages of T lymphocytes diverge d uring the course of the beta-, gamma- and delta-chain rearrangement of T-ce ll 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 p re-TCR alpha protein, which is present in immature but not in mature T cell s 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 gamm a 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 obse rvations are consistent with the idea that different signals emanating from the gamma delta TCR and pre-TCR instruct lineage commitment(8). Here we sh ow, by using confocal microscopy and biochemistry to analyse the initiation of signalling, that the pre-TCR but not the gamma delta TCR colocalizes wi th the p56(lck) Src kinase into glycolipid-enriched membrane domains (rafts ) apparently without any need for ligation. This results in the phosphoryla tion of CD3 epsilon and Zap-70 signal transducing molecules. The results in dicate clear differences between pre-TCR and gamma delta TCR signalling.