Different initiation of pre-TCR and γδTCR signalling

Lineage choice is of great interest in developmental biology. In the immune system, the αβ and γδ lineages of T lymphocytes diverge during the course of the β-, γ- and δ-chain rearrangement of T-cell receptor (TCR) genes that takes place within the same precursor cell and which results in the formation of the γδTCR or pre-TCR proteins1,2,3. The pre-TCR consists of the TCRβ chain covalently linked to the pre-TCRα protein, which is present in immature but not in mature T cells which instead express the TCRα chain4,5. Animals deficient in pre-TCRα have few αβ lineage cells but an increased number of γδ T cells. These γδ T cells exhibit more extensive TCRβ rearrangement than γδ T cells from wild-type mice6,7. These observations are consistent with the idea that different signals emanating from the γδTCR and pre-TCR instruct lineage commitment8. Here we show, by using confocal microscopy and biochemistry to analyse the initiation of signalling, that the pre-TCR but not the γδTCR colocalizes with the p56lck Src kinase into glycolipid-enriched membrane domains (rafts) apparently without any need for ligation. This results in the phosphorylation of CD3ε and Zap-70 signal transducing molecules. The results indicate clear differences between pre-TCR and γδTCR signalling.