Identification Of The Pre-T-Cell Receptor A Chain In Nonmammalian Vertebrates Challenges The Structure-Function Of The Molecule

In humans and mice, the early development of alpha beta T cells is controlled by the pre-T-cell receptor a chain (pT alpha) that is covalently associated with the T-cell receptor beta (TCR beta) chain to form the pre-T-cell receptor (pre-TCR) at the thymocyte surface. Pre-TCR functions in a ligand-independent manner through self-oligomerization mediated by pT alpha. Using in silico and gene synteny-based approaches, we identified the pT alpha gene (PTCRA) in four sauropsid (three birds and one reptile) genomes. We also identified 25 mammalian PTCRA sequences now covering all mammalian lineages. Gene synteny around PTCRA is remarkably conserved in mammals but differences upstream of PTCRA in sauropsids suggest chromosomal rearrangements. PTCRA organization is highly similar in sauropsids and mammals. However, comparative analyses of the pT alpha functional domains indicate that sauropsids, monotremes, marsupials, and lagomorphs display a short pT alpha cytoplasmic tail and lack most residues shown to be critical for human and murine pre-TCR self-oligomerization. Chicken PTCRA transcripts similar to those in mammals were detected in immature double-negative and double-positive thymocytes. These findings give clues about the evolution of this key molecule in amniotes and suggest that the ancestral function of pT alpha was exclusively to enable expression of the TCR beta chain at the thymocyte surface and to allow binding of pre-TCR to the CD3 complex. Together, our data provide arguments for revisiting the current model of pT alpha signaling.