Efficient presentation of both cytosolic and endogenous transmembrane protein antigens on MHC class II is dependent on cytoplasmic proteolysis

P. Mukherjee, A. Dani, S. Bhatia, Nagendra Singh, A. Y. Rudensky, A. George, V. Bal, S. Mayor, S. Rath

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Peptides from extracellular proteins presented on MHC class II are mostly generated and loaded in endolysosomal compartments, but the major pathways responsible for loading peptides from APC-endogenous sources on MHC class II are as yet unclear. In this study, we show that MHC class II molecules present peptides from proteins such as OVA or conalbumin introduced into the cytoplasm by hyperosmotic pinosome lysis, with efficiencies comparable to their presentation via extracellular fluid-phase endocytosis. This cytosolic presentation pathway is sensitive to proteasomal inhibitors, whereas the presentation of exogenous Ags taken up by endocytosis is not. Inhibitors of nonproteasomal cytosolic proteases can also inhibit MHC class II-restricted presentation of cytosolically delivered protein, without inhibiting MHC class I-restricted presentation from the same protein. Cytosolic processing of a soluble fusion protein containing the peptide epitope I-Eα52-68 yields an epitope that is similar to the one generated during constitutive presentation of I-Eα as an endogenous transmembrane protein, but is subtly different from the one generated in the exogenous pathway. Constitutive MHC class II-mediated presentation of the endogenous transmembrane protein I-Eα is also specifically inhibited over time by inhibitors of cytosolic proteolysis. Thus, Ag processing in the cytoplasm appears to be essential for the efficient presentation of endogenous proteins, even transmembrane ones, on MHC class II, and the proteolytic pathways involved may differ from those used for MHC class I-mediated presentation.

Original languageEnglish (US)
Pages (from-to)2632-2641
Number of pages10
JournalJournal of Immunology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

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Proteolysis
Antigens
Proteins
Peptides
Endocytosis
Epitopes
Cytoplasm
Conalbumin
Extracellular Fluid
Peptide Hydrolases

ASJC Scopus subject areas

  • Immunology

Cite this

Efficient presentation of both cytosolic and endogenous transmembrane protein antigens on MHC class II is dependent on cytoplasmic proteolysis. / Mukherjee, P.; Dani, A.; Bhatia, S.; Singh, Nagendra; Rudensky, A. Y.; George, A.; Bal, V.; Mayor, S.; Rath, S.

In: Journal of Immunology, Vol. 167, No. 5, 01.09.2001, p. 2632-2641.

Research output: Contribution to journalArticle

Mukherjee, P. ; Dani, A. ; Bhatia, S. ; Singh, Nagendra ; Rudensky, A. Y. ; George, A. ; Bal, V. ; Mayor, S. ; Rath, S. / Efficient presentation of both cytosolic and endogenous transmembrane protein antigens on MHC class II is dependent on cytoplasmic proteolysis. In: Journal of Immunology. 2001 ; Vol. 167, No. 5. pp. 2632-2641.
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