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Citation
Tags
HERO ID
1073259
Reference Type
Journal Article
Subtype
Review
Title
Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression
Author(s)
Busch, R; Rinderknecht, CH; Roh, S; Lee, AW; Harding, JJ; Burster, T; Hornell, TM; Mellins, ED
Year
2005
Is Peer Reviewed?
Yes
Journal
Immunological reviews
ISSN:
0105-2896
EISSN:
1600-065X
Volume
207
Page Numbers
242-260
Language
English
PMID
16181341
DOI
10.1111/j.0105-2896.2005.00306.x
Web of Science Id
WOS:000232048300020
Abstract
In antigen-presenting cells (APCs), loading of major histocompatibility complex class II (MHC II) molecules with peptides is regulated by invariant chain (Ii), which blocks MHC II antigen-binding sites in pre-endosomal compartments. Several molecules then act upon MHC II molecules in endosomes to facilitate peptide loading: Ii-degrading proteases, the peptide exchange factor, human leukocyte antigen-DM (HLA-DM), and its modulator, HLA-DO (DO). Here, we review our findings arguing that DM stabilizes a globally altered conformation of the antigen-binding groove by binding to a lateral surface of the MHC II molecule. Our data imply changes in the interactions between specificity pockets and peptide side chains, complementing data from others that suggest DM affects hydrogen bonds. Selective weakening of peptide/MHC interactions allows DM to alter the peptide repertoire. We also review our studies in cells that highlight the ability of several factors to modulate surface expression of MHC II molecules via post-Golgi mechanisms; these factors include MHC class II-associated Ii peptides (CLIP), DM, and microbial products that modulate MHC II traffic from endosomes to the plasma membrane. In this context, we discuss possible mechanisms by which the association of some MHC II alleles with autoimmune diseases may be linked to their low CLIP affinity.
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