Abstract
Assembly of the multisubunit T cell antigen receptor (TCR) complex is an intricate process requiring coordinated regulation of at least six different gene products (alpha, beta, gamma, delta, epsilon, and zeta) and the ordered pairing of partner chains within the endoplasmic reticulum (ER). To date, two proteins have been implicated as functioning as molecular chaperones in the assembly of nascent TCR proteins: calnexin, a resident ER transmembrane protein, which associates with all TCR components except zeta, and T cell receptor-associated protein, which selectively associates with CD3gammaepsilon pairs. In this study, we examined the association of calreticulin, a soluble protein with significant sequence homology to calnexin, with newly synthesized TCR proteins. Analogous to calnexin, processing of glycan chains by glucosidase enzymes was required for initial association of TCRalpha and -beta proteins with calreticulin; however, several major differences were noted regarding interaction of calnexin and calreticulin chaperones with TCR proteins. First, TCRalpha and -beta proteins showed prolonged association with calnexin molecules compared with calreticulin; interaction of TCRalpha proteins with calreticulin was particularly transient, with most calreticulin-TCRalpha protein complexes dissociating within 15 min of their initial assembly. Second, we found that, unlike calnexin, which associated with clonotypic TCRalpha and -beta proteins and invariant CD3delta and -epsilon polypeptides, calreticulin associated specifically with clonotypic TCRalpha and -beta proteins. These studies identify calreticulin as a molecular chaperone for nascent clonotypic TCRalpha and -beta proteins and demonstrate that calreticulin and calnexin differentially associate with newly synthesized TCR proteins within the ER.
Highlights
Tor complexes, including major histocompatibility class I molecules [4, 6, 7], class II molecules [8], and the B cell antigen receptor [4, 9]
These studies demonstrate that, analogous to calnexin, glycan processing is required for assembly of calreticulin with T cell antigen receptor (TCR)␣ and - proteins in the endoplasmic reticulum (ER), that nascent TCR␣ and - proteins are more stably associated with calnexin than with calreticulin, and FIG. 5
Similar to what has been observed with calnexin [5], we found that Glc trimming was necessary for efficient association of newly synthesized TCR␣ and - proteins with calreticulin
Summary
Vol 271, No 41, Issue of October 11, pp. 25345–25349, 1996 Printed in U.S.A. The Related Molecular Chaperones Calnexin and Calreticulin Differentially Associate with Nascent T Cell Antigen Receptor Proteins within the Endoplasmic Reticulum*. Of the multisubunit T cell antigen receptor (TCR) complex is an intricate process requiring coordinated regulation of at least six different gene products (␣, , ␥, ␦, ⑀, and ) and the ordered pairing of partner chains within the endoplasmic reticulum (ER). Analogous to calnexin, processing of glycan chains by glucosidase enzymes was required for initial association of TCR␣ and - proteins with calreticulin; several major differences were noted regarding interaction of calnexin and calreticulin chaperones with TCR proteins. We found that, unlike calnexin, which associated with clonotypic TCR␣ and - proteins and invariant CD3␦ and -⑀ polypeptides, calreticulin associated with clonotypic TCR␣ and - proteins These studies identify calreticulin as a molecular chaperone for nascent clonotypic TCR␣ and - proteins and demonstrate that calreticulin and calnexin differentially associate with newly synthesized TCR proteins within the ER. In contrast to calnexin, which associated with both clonotypic TCR␣ and - proteins and invariant CD3␦ and -⑀ chains, we found that calreticulin assembly was restricted to clonotypic, antigen-reactive TCR␣ and - chains
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
