Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO

van Ham, M., van Lith, M., Lillemeier, B., Tjin, E., Gruneberg, U., Rahman, D., Pastoors, L., van Meijgaarden, K., Roucard, C., Trowsdale, J., Ottenhoff, T., Pappin, D., Neefjes, J. (April 2000) Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO. J Exp Med, 191 (7). pp. 1127-36. ISSN 0022-1007 (Print)0022-1007 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10748231
DOI: 10.1084/jem.191.7.1127

Abstract

Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most class II alleles, peptide binding depends on the catalytic action of human histocompatibility leukocyte antigens (HLA)-DM. HLA-DO is selectively expressed in B cells and impedes the activity of DM, yet its physiological role remains unclear. Cell surface iodination assays and mass spectrometry of major histocompatibility complex class II-eluted peptides show that DO affects the antigenic peptide repertoire of class II. DO generates both quantitative and qualitative differences, and inhibits presentation of large-sized peptides. DO function was investigated under various pH conditions in in vitro peptide exchange assays and in antigen presentation assays using DO(-) and DO(+) transfectant cell lines as antigen-presenting cells, in which effective acidification of the endocytic pathway was prevented with bafilomycin A(1), an inhibitor of vacuolar ATPases. DO effectively inhibits antigen presentation of peptides that are loaded onto class II in endosomal compartments that are not very acidic. Thus, DO appears to be a unique, cell type-specific modulator mastering the class II-mediated immune response induced by B cells. DO may serve to increase the threshold for nonspecific B cell activation, restricting class II-peptide binding to late endosomal compartments, thereby affecting the peptide repertoire.

Item Type: Paper
Uncontrolled Keywords: Antigen Presentation/ immunology Antigens, Differentiation, B-Lymphocyte/immunology B-Lymphocytes/immunology HLA-D Antigens/genetics/ immunology Histocompatibility Antigens Class II/immunology Humans Hydrogen-Ion Concentration Peptides/immunology Recombinant Fusion Proteins/genetics/immunology Tumor Cells, Cultured
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells

bioinformatics > genomics and proteomics
Investigative techniques and equipment > spectroscopy > mass spectrometry
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 3 April 2000
Date Deposited: 30 Jan 2014 21:17
Last Modified: 30 Jan 2014 21:17
PMCID: PMC2193174
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29418

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