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Kinetic analysis of peptide loading onto HLA-DR molecules mediated by HLA-DM.

The nonclassical major histocompatibility complex class II molecule HLA-DM (DM) has recently been shown to play a central role in the class II-associated antigen presentation pathway: DM releases invariant chain-derived CLIP peptides (class II-associated invariant chain protein peptide) from HLA-DR...

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Bibliographic Details
Main Authors: Vogt, Anne B. (Author) , Kropshofer, Harald (Author) , Moldenhauer, Gerhard (Author) , Hämmerling, Günter J. (Author)
Format: Article (Journal)
Language:English
Published: September 3, 1996
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 1996, Volume: 93, Issue: 18, Pages: 9724-9729
ISSN:1091-6490
DOI:10.1073/pnas.93.18.9724
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.93.18.9724
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/doi/10.1073/pnas.93.18.9724
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Author Notes:Anne B. Vogt, Harald Kropshofer, Gerhard Moldenhauer, and Günter J. Hämmerling
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Summary:The nonclassical major histocompatibility complex class II molecule HLA-DM (DM) has recently been shown to play a central role in the class II-associated antigen presentation pathway: DM releases invariant chain-derived CLIP peptides (class II-associated invariant chain protein peptide) from HLA-DR (DR) molecules and thereby facilitates loading with antigenic peptides. Some observations have led to the suggestion that DM acts in a catalytic manner, but so far direct proof is missing. Here, we investigated in vitro the kinetics of exchange of endogenously bound CLIP for various peptides on DR1 and DR2a molecules: we found that in the presence of DM the peptide loading process follows Michaelis-Menten kinetics with turnover numbers of 3-12 DR molecules per minute per DM molecule, and with KM values of 500-1000 nM. In addition, surface plasmon resonance measurements showed that DM interacts efficiently with DR-CLIP complexes but only weakly with DR-peptide complexes isolated from DM-positive cells. Taken together, our data provide evidence that DM functions as an enzyme-like catalyst of peptide exchange and favors the generation of long-lived DR-peptide complexes that are no longer substrates for DM.
Item Description:Gesehen am 23.07.2025
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.93.18.9724

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