Modification of the T cell antigen-receptor (TCR) complex by UDP-glucose :glycoprotein glucosyltransferase - TCR folding is finalized convergent with formation of alpha beta delta epsilon gamma epsilon complexes

Most T lymphocytes express on their surfaces a multisubunit receptor comple x, the T cell antigen receptor (TCR) containing alpha, beta, gamma, delta, epsilon, and zeta molecules, that has been widely studied as a model system for protein quality control. Although the parameters of TCR assembly are r elatively well established, little information exists regarding the stage(s ) of TCR oligomerization where folding of TCR proteins is completed. Here w e evaluated the modification of TCR glycoproteins by the endoplasmic reticu lum folding sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (GT) as a unique and sensitive indicator of how TCR subunits assembled into mul tisubunit; complexes are perceived by the endoplasmic reticulum quality con trol system. These results demonstrate that all TCR subunits containing N-g lycan were modified by GT and that TCR proteins were differentially regluco sylated during their assembly with partner TCR chains. importantly, these d ata show that GT modification of most TCR subunits persisted until as; semb ly of CD3 alpha beta chains and formation of CD3-associated, disulfide-link ed alpha beta heterodimers. These studies provide a novel evaluation of the folding status of TCR glycoproteins during their assembly into multisubuni t complexes and are consistent with the concept that TCR folding is finaliz ed convergent with formation of alpha beta delta epsilon gamma epsilon comp lexes.