International Immunology, Vol. 11, No. 1, 99-111,
January 1999
© 1999 Japanese Society for Immunology
Cellular distribution of a mixed MHC class II heterodimer between DR
and a chimeric DOß chain
1 Laboratories of Immunogenetics and Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
2 Laboratory of Analytical Immunochemistry, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France
Correspondence to: J. Thibodeau, Laboratory of Molecular Immunology, Department of Microbiology and Immunology, University of Montreal, CP 6128, Succ. Centre-Ville, Montreal, Quebec H3C 3J7, Canada
Human MHC class II antigens include HLA-DR, -DQ, and -DP molecules that present antigens to CD4+ T cells, as well as the non-classical molecules HLA-DM and -DO. HLA-DM promotes peptide binding to class II molecules in endocytic compartments and HLA-DO, which is physically associated with HLA-DM in B lymphocytes, regulates HLA-DM function. Antibodies specific for the DOß chain were obtained by immunization of mice with a heterodimer consisting of a chimeric DOß chain (DR/DOß), containing 18 N-terminal residues of DRß, paired with the DR
chain and isolated from transfected murine fibroblasts. The specificity of this serum for the DOß chain and the lysosomal expression of the HLA-DO protein was confirmed using mutant human B cell lines lacking DR or DO molecules. The lysosomal localization of HLA-DO in human B cells contrasts with the cell surface expression of the mixed pair in transfected murine fibroblasts and raises questions concerning the role of the putative targeting motifs in HLA-DO. Transfection of the chimeric DR/DOß chain along with DR into human epithelial HeLa cells resulted in high levels of expression of the mixed isotypic pair at the surface of transfectants as well as in lysosomes. The same pattern was observed in HeLa cells transfected with the DOß chimera and a DR chain lacking the cytoplasmic tail. Taken together, these results suggest that functional sorting motifs exist in the DOß chain but that the tight compartmentalization of HLA-DO observed inside B lymphocytes is controlled by the HLA-DO chain and HLA-DM.
Keywords: class II, DR, DOß, MHC
The first two authors contributed equally to this work
Transmitting editor: K. Eichmann
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