Structural and functional characterization of HLA-DR molecules circulating in the serum.
HLA molecules are highly polymorphic glycoproteins with a single binding site for immunogenic peptides. The complex formed by HLA-DR molecules and peptides is the entity specifically recognized by the antigen receptor of CD4+ helper T lymphocytes. This biological function has been linked to the constitutive cell surface expression of HLA molecules on antigen-presenting cells which provide immunogenic peptides through denaturation or fragmentation of antigen. Here, we report that HLA-DR molecules can be identified in a soluble form circulating in the serum. Biochemical characterization and recognition of such soluble HLA-DR molecules by a monoclonal antibody reactive to conformational determinants on the alpha-beta HLA complex indicates that they are circulating as intact heterodimers. Upon activation, human T cells and B cells release soluble HLA-DR molecules. The expression and secretion of HLA-DR by T lymphocytes is greatly enhanced in the presence of macrophages indicating that the production of HLA-DR molecules might be regulated and controlled through factors derived from antigen-presenting cells. An alloreactive human T cell clone can be stimulated to proliferate in response to soluble HLA-DR molecules purified and enriched from serum suggesting that the soluble form of the natural ligand of the T cell receptor might have immunoregulatory functions.
Department of Medicine, University of Heidelberg.
M
M
Jendro
J J
JJ
Goronzy
C M
CM
Weyand
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D006684:HLA-DR Antigens; D010835:Phytohemagglutinins