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Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens

Record type: Article

Cytoplasmic Ags derived from viruses, cytosolic bacteria, tumors, and allografts are presented to T cells by MHC class I or class II molecules. In the case of class II-restricted Ags, professional APCs acquire them during uptake of dead class II-negative cells and present them via a process called indirect presentation. It is generally assumed that the cytosolic Ag-processing machinery, which supplies peptides for presentation by class I molecules, plays very little role in indirect presentation of class II-restricted cytoplasmic Ags. Remarkably, upon testing this assumption, we found that proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with Ag processing, but not tapasin, partially destroyed or removed cytoplasmic class II-restricted Ags, such that their inhibition or deficiency led to dramatically increased Th cell responses to allograft (HY) and microbial (Listeria monocytogenes) Ags, both of which are indirectly presented. This effect was neither due to enhanced endoplasmic reticulum-associated degradation nor competition for Ag between class I and class II molecules. From these findings, a novel model emerged in which the cytosolic Ag-processing machinery regulates the quantity of cytoplasmic peptides available for presentation by class II molecules and, hence, modulates Th cell responses.

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Citation

Dragovic, Srdjan M., Hill, Timothy, Christianson, Gregory J., Kim, Sungjune, Elliott, Tim, Scott, Diane, Roopenian, Derry C., Van Kaer, Luc and Joyce, Sebastian (2011) Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens Journal of Immunology, 186, (12), pp. 6683-6692. (doi:10.4049/jimmunol.1100525). (PMID:21572029).

More information

Published date: 13 May 2011
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 337326
URI: http://eprints.soton.ac.uk/id/eprint/337326
ISSN: 0022-1767
PURE UUID: d52c4484-cd29-438f-aef3-80ae95e1a721
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 24 Apr 2012 11:30
Last modified: 18 Jul 2017 06:03

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Contributors

Author: Srdjan M. Dragovic
Author: Timothy Hill
Author: Gregory J. Christianson
Author: Sungjune Kim
Author: Tim Elliott ORCID iD
Author: Diane Scott
Author: Derry C. Roopenian
Author: Luc Van Kaer
Author: Sebastian Joyce

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