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'Chemical analogues' of HLA-DM can induce a peptide-receptive state in HLA-DR molecules

Item Type:Article
Title:'Chemical analogues' of HLA-DM can induce a peptide-receptive state in HLA-DR molecules
Creators Name:Marin-Esteban, V. and Falk, K. and Roetzschke, O.
Abstract:We had recently identified small molecular compounds that are able to accelerate the ligand exchange reactions of HLA-DR molecules. Here we show that this acceleration is due to the induction of a "peptide-receptive" state. Dissociation experiments of soluble HLA-DR2-CLIP (class II-associated invariant chain peptide) complex and peptide-binding studies with "nonreceptive" empty HLA-DR1 and -DR2 molecules revealed that the presence of a small phenolic compound carrying an H-bond donor group (-OH) results in the drastic increase of both off- and on-rates. The rate-limiting step for ligand exchange, the transition of the major histocompatibility complex molecule from a nonreceptive into the receptive state, is normally mediated by interaction with the chaperone HLA-DM. In this respect, the effect of small molecules resembles that of the natural catalyst, except that they are still active at neutral pH. These "chemical analogues" of HLA-DM can therefore modulate the response of CD4+ T cells by editing the antigen composition of surface-bound class II major histocompatibility complex on living antigen-presenting cells.
Keywords:Antigen Presentation, Antigens, CD4-Positive T-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Fibroblasts, HLA-D Antigens, HLA-DR Antigens, Hydrogen-Ion Concentration, Kinetics, Ligands, MHC Class II Genes, Chemical Models, Peptides, Phenol, Protein Binding, Recombinant Proteins, Surface Plasmon Resonance, Time Factors, Animals, Mice
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:50684-50690
Date:20 September 2004
Official Publication:https://doi.org/10.1074/jbc.M407598200
PubMed:View item in PubMed

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