Importance of the T cell receptor alpha-chain transmembrane distal region for assembly with cognate subunits

Antigen recognition by alpha beta T lymphocytes is mediated via the multisu bunit TCR complex consisting of invariant CD gamma,delta,epsilon and chains associated with clonotypic TCR alpha and P molecules. Charged amino acids located centrally within the TCR alpha transmembrane region are necessary a nd sufficient for assembly with the CD3 delta epsilon heterodimer. Previous ly, we have shown that deletion of 6-12 amino acids from the carboxy termin us of the TCR alpha -chain dramatically abrogates surface TCR expression, s uggesting that the distal portion of the TCR alpha transmembrane region con tains information that regulates the assembly and/or intracellular transpor t of TCR complexes. We have examined in more detail the molecular basis for reduced TCR expression in T cells bearing truncated TCR alpha chains. We f ound that in contrast to wild-type (wt), variant TCR alpha proteins missing the last nine C-terminal amino acids did not associate with core CD3 gamma ,delta,epsilon chains and were not assembled into disulphide-linked ap hete rodimers. The stability of newly synthesised wt and variant TCR alpha molec ules was similar, showing that the abrogated surface TCR expression was not a consequence of impaired protein survival. Nevertheless, truncated TCR al pha chains still assembled with the chaperon protein calnexin in the endopl asmic reticulum, indicating that the distal portion of the TCR alpha transm embrane region is not essential for calnexin interaction. These data docume nt a role for the distal portion of the TCR alpha transmembrane region in t he assembly of TCR complexes and provide a molecular basis for reduced TCR expression in cells bearing truncated TCR alpha chains. (C) 2001 Elsevier S cience Ltd. All rights reserved.