Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens

Michael S. Marks, Janice Blum, Peter Cresswell

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

HLA class II antigens are heterodimeric cell surface glycoproteins that interact with antigenic peptides to form complexes recognizable by CD4-positive T cells. During their biosynthesis, class II antigens are retained in a post-Golgi compartment in association with the invariant chain, which dissociates before class II cell surface expression. To address whether the invariant chain mediates this post-Golgi retention, its transport and assembly were examined in cells that do not express HLA class II antigens. Pulsechase analysis and endoglycosidase digestions showed that very little invariant chain proceeded as far as the frans-Golgi in class II-negative cell lines. Immunofluorescence studies suggested that in these cells the invariant chain is sequestered in the RER. Gel filtration and cross-linking data showed that RER-localized invariant chain is present as trimers or aggregated trimers. Multimerization is mediated by lumenal interactions; a proteolytic fragment of the invariant chain corresponding to the lumenal domain remained trimeric as determined by cross-linking analysis. Similar transport and structural characteristics were observed for a pool of excess invariant chain in class II-positive cells, suggesting that an excess of invariant chain in the ER may be important for class II antigen function. These results have important implications for the transport of cellular proteins in general and for the role of the invariant chain in class II antigen biosynthesis.

Original languageEnglish (US)
Pages (from-to)839-855
Number of pages17
JournalJournal of Cell Biology
Volume111
Issue number3
StatePublished - Sep 1990
Externally publishedYes

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Rough Endoplasmic Reticulum
Histocompatibility Antigens Class II
HLA Antigens
invariant chain
Glycoside Hydrolases
Membrane Glycoproteins
Gel Chromatography
Fluorescent Antibody Technique
Digestion
Carrier Proteins
T-Lymphocytes
Cell Line
Peptides

ASJC Scopus subject areas

  • Cell Biology

Cite this

Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens. / Marks, Michael S.; Blum, Janice; Cresswell, Peter.

In: Journal of Cell Biology, Vol. 111, No. 3, 09.1990, p. 839-855.

Research output: Contribution to journalArticle

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