HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading

van Ham, S. M., Tjin, E. P., Lillemeier, B. F., Gruneberg, U., van Meijgaarden, K. E., Pastoors, L., Verwoerd, D., Tulp, A., Canas, B., Rahman, D., Ottenhoff, T. H., Pappin, D. J., Trowsdale, J., Neefjes, J. (1997) HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading. Curr Biol, 7 (12). pp. 950-7. ISSN 0960-9822 (Print)0960-9822 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9382849
DOI: 10.1016/S0960-9822(06)00414-3

Abstract

BACKGROUND: Class II molecules of the major histocompatibility complex become loaded with antigenic peptides after dissociation of invariant chainderived peptides (CLIP) from the peptide-binding groove. The human leukocyte antigen (HLA)-DM is a prerequisite for this process, which takes place in specialised intracellular compartments. HLA-DM catalyses the peptide-exchange process, simultaneously functioning as a peptide 'editor', favouring the presentation of stably binding peptides. Recently, HLA-DO, an unconventional class II molecule, has been found associated with HLA-DM in B cells, yet its function has remained elusive. RESULTS: The function of the HLA-DO complex was investigated by expression of both chains of the HLA-DO heterodimer (either alone or fused to green fluorescent protein) in human Mel JuSo cells. Expression of HLA-DO resulted in greatly enhanced surface expression of CLIP via HLA-DR3, the conversion of class II complexes to the SDS-unstable phenotype and reduced antigen presentation to T-cell clones. Analysis of peptides eluted from HLA-DR3 demonstrated that CLIP was the major peptide bound to class II in the HLA-DO transfectants. Peptide exchange assays in vitro revealed that HLA-DO functions directly at the level of class II peptide loading by inhibiting the catalytic action of HLA-DM. CONCLUSIONS: HLA-DO is a negative modulator of HLA-DM. By stably associating with HLA-DM, the catalytic action of HLA-DM on class II peptide loading is inhibited. HLA-DO thus affects the peptide repertoire that is eventually presented to the immune system by MHC class II molecules.

Item Type: Paper
Additional Information: van Ham, S M Tjin, E P Lillemeier, B F Gruneberg, U van Meijgaarden, K E Pastoors, L Verwoerd, D Tulp, A Canas, B Rahman, D Ottenhoff, T H Pappin, D J Trowsdale, J Neefjes, J Research Support, Non-U.S. Gov't England Current biology : CB Curr Biol. 1997 Dec 1;7(12):950-7.
Uncontrolled Keywords: Amino Acid Sequence Antigen Presentation Antigens, Differentiation, B-Lymphocyte/metabolism Cell Line HLA-D Antigens/genetics/ metabolism HLA-DR3 Antigen/metabolism Histocompatibility Antigens Class II/ metabolism Humans Molecular Sequence Data Recombinant Fusion Proteins/genetics/metabolism Transfection
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line

organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation
Investigative techniques and equipment > transfection
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Kathleen Darby
Date Deposited: 07 May 2014 14:43
Last Modified: 07 May 2014 14:43
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30023

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