Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation Journal Article

  


Authors: Fallas, J. L.; Tobin, H. M.; Lou, O.; Guo, D.; Sant'angelo, D. B.; Denzin, L. K.
Article Title: Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation
Abstract: The MHC class II-like molecule HLA-DM (DM) (H-2M in mice) catalyzes the exchange of CLIP for antigenic peptides in the endosomes of APCs. HLA-DO (DO) (H-2O in mice) is another class II-like molecule that is expressed in B cells, but not in other APCs. Studies have shown that DO impairs or modifies the peptide exchange activity of DM. To further evaluate the role of DO in Ag processing and presentation, we generated transgenic mice that expressed the human HLA-DOA and HLA-DOB genes under the control of a dendritic cell (DC)-specific promoter. Our analyses of DCs from these mice showed that as DO levels increased, cell surface levels of Ab-CLIP also increased while class II-peptide levels decreased. The presentation of some, but not all, exogenous Ags to T cells or T hybridomas was significantly inhibited by DO. Surprisingly, H-2M accumulated in DO-expressing DCs and B cells, suggesting that H-2O/DO prolongs the half-life of H-2M. Overall, our studies showed that DO expression impaired H-2M function, resulting in Ag-specific down-modulation of class II Ag processing and presentation.
Keywords: promoter region; nonhuman; antigen expression; animal cell; mouse; animals; mice; cells, cultured; dendritic cell; embryo; mice, inbred c57bl; transgenic mouse; b-lymphocytes; mice, transgenic; antigen presentation; dendritic cells; antigens; recombinant fusion proteins; major histocompatibility antigen class 2; antigen recognition; peptide fragments; gene control; immunomodulation; hybridoma; actins; histocompatibility antigens class ii; hla do antigen; hla-d antigens; antigens, cd11c; promoter regions (genetics); antigens, differentiation, b-lymphocyte; hybridomas; genes, synthetic; ovalbumin; muramidase; h-2 antigens; humans; priority journal; article; beta 2-microglobulin
Journal Title: Journal of Immunology
Volume: 173
Issue: 3
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2004-08-01
Start Page: 1549
End Page: 1560
Language: English
PROVIDER: scopus
PUBMED: 15265882
DOI: 10.4049/jimmunol.173.3.1549
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-3242772752&partnerID=40&md5=413c0d10ffdc3f8a2db7291fbe0a726f
Notes: J. Immunol. -- Cited By (since 1996):32 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 15265882 -- Source: Scopus
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MSK Authors
  1. Lisa K Denzin
    22 Denzin
  2. Derek B Sant'angelo
    46 Sant'angelo
  3. Donglin Guo
    4 Guo
  4. Helen Tobin
    5 Tobin
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