Expression of secreted and glycosylphosphatidylinositol-bound Qa-2 molecules is dependent on functional TAP-2 peptide transporter

Piotr Tabaczewski, Iwona Stroynowski

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The assembly of class Ia MHC Ags is thought to occur in the endoplasmic reticulum (ER) where H chains, β2m, and peptides come together to form trimers. Several types of proteins are implicated in the regulation of class Ia MHC assembly, including: 1) TAP1/TAP2 transporters, which translocate peptides derived from naturally processed endogenous proteins from the cytosol into the ER and which are necessary for expression of 'peptide- filled' class Ia Ags, and 2) calnexin, a chaperone protein, which was proposed to retain unassembled class Ia chains in the ER. In our study, we examined if the expression of class Ib Qa-2 molecules depends on the TAP1/TAP2 peptide delivery system. The glycosylphosphatidylinositol-linked GPIQa-2 and soluble SQa-2 molecules lack transmembrane regions and consensus calnexin binding sites. Because of these structural features, they were thought to differ from class Ia Ags in cellular trafficking pathways and peptide-binding mechanisms. We find that in TAP2 negative RMA-S cells, the great majority of GPIQa-2 and SQa-2 behave as 'empty' heterodimers: They cannot maintain stable conformations at 37°C, but their half-lives can be significantly extended by reducing the temperature to 26°C. These results suggest that the Qa-2 binding peptides are delivered to Qa-2 molecules in a manner similar to the class Ia MHC Ag system and, therefore, that both GPIQa- 2 and SQa-2 may be assembled in the ER. Detection of a small population of heat-resistant Qa-2 molecules in RMA-S is indicative of an alternative, but minor, peptide delivery pathway, or 'leakiness' of the RMA-S mutation.

Original languageEnglish (US)
Pages (from-to)5268-5274
Number of pages7
JournalJournal of Immunology
Volume152
Issue number11
StatePublished - Jun 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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