Positive Selection Through a Motif in the αβ T Cell Receptor

The two lineages of T cells, αβ and γδ, differ in their developmental requirements: only αβ T cells require major histocompatibility complex recognition, a process known as positive selection. The αβ T cell receptor (TCR), but not its γδ counterpart, contains a motif within the α-chain connecting peptide domain (α-CPM) that has been conserved over the last 500 million years. In transgenic mice expressing an αβ TCR lacking the α-CPM, thymocytes were blocked in positive selection but could undergo negative selection. Thus, the α-CPM seems to participate in the generation of signals required for positive selection.