Distinct functions for the glycans of tapasin and heavy chains in the assembly of MHC class I molecules

Syed Monem Rizvi, Natasha Del Cid, Lonnie Lybarger, Malini Raghavan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Complexes of specific assembly factors and generic endoplasmic reticulum (ER) chaperones, collectively called the MHC class I peptide-loading complex (PLC), function in the folding and assembly of MHC class I molecules. The glycan-binding chaperone calreticulin (CRT) and partner oxidoreductase ERp57 are important in MHC class I assembly, but the sequence of assembly events and specific interactions involved remain incompletely understood. We show that the recruitments of CRT and ERp57 to the PLC are codependent and also dependent upon the ERp57 binding site and the glycan of the assembly factor tapasin. Furthermore, the ERp57 binding site and the glycan of tapasin enhance β2m and MHC class I heavy (H) chain recruitment to the PLC, with the ERp57 binding site having the dominant effect. In contrast, the conserved MHC class I H chain glycan played a minor role in CRT recruitment into the PLC, but impacted the recruitment of H chains into the PLC, and glycan-deficient H chains were impaired for tapasin-independent and tapasin-assisted assembly. The conserved MHC class I glycan and tapasin facilitated an early step in the assembly of H chain-β2m heterodimers, for which tapasin-ERp57 or tapasin-CRT complexes were not required. Together, these studies provide insights into how PLCs are constructed, demonstrate two distinct mechanisms by which PLCs can be stabilized, and suggest the presence of intermediate H chain-deficient PLCs.

Original languageEnglish (US)
Pages (from-to)2309-2320
Number of pages12
JournalJournal of Immunology
Volume186
Issue number4
DOIs
StatePublished - Feb 15 2011

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Polysaccharides
Calreticulin
Peptides
Binding Sites
tapasin
Endoplasmic Reticulum
Oxidoreductases

ASJC Scopus subject areas

  • Immunology

Cite this

Distinct functions for the glycans of tapasin and heavy chains in the assembly of MHC class I molecules. / Rizvi, Syed Monem; Del Cid, Natasha; Lybarger, Lonnie; Raghavan, Malini.

In: Journal of Immunology, Vol. 186, No. 4, 15.02.2011, p. 2309-2320.

Research output: Contribution to journalArticle

Rizvi, Syed Monem ; Del Cid, Natasha ; Lybarger, Lonnie ; Raghavan, Malini. / Distinct functions for the glycans of tapasin and heavy chains in the assembly of MHC class I molecules. In: Journal of Immunology. 2011 ; Vol. 186, No. 4. pp. 2309-2320.
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