Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes.
MICA is a new, highly divergent and polymorphic HLA-related gene that has a similar intron-exon organization as the HLA class I genes. It functions as a restriction element for intestinal gammadeltaT cells and it behaves as a cell stress molecule. It is likely that the polymorphic MICA molecule may be target for specific antibodies and T cells in solid organ grafts or in graft versus host disease (GVHD). Previously, we generated three MICA-specific sera in rabbits, which were used for Western blot, flow cytometry and immunoprecipitation. We demonstrated that MICA is expressed in endothelial cells, keratinocyes and monocytes, but not in CD4+, CD8+ or CD19+ lymphocytes. We also found that MICA is expressed on the cell surface in HeLa cells. In the present work, performing peptide neutralization assays, we further confirmed the specificity of the reactivity of these sera against MICA. Also, by Western blot we demonstrate that freshly isolated human skin-derived fibroblasts express MICA. We also investigated the surface expression of MICA in different, freshly-isolated cells. The results show that endothelial cells and fibroblasts express MICA at the cell surface. Although expressing the 62 kDa MICA band, as detected by Western blots, keratinocytes and monocytes do not seem to express this antigen on the cell membrane. This differential surface expression of MICA by endothelial cells and fibroblasts vs. keratinocytes and monocytes, may indicate that the levels of surface MICA are differentially regulated in different cells. Moreover, the expression of MICA on the surface of endothelial cells makes this polymorphic molecule a possible target during the immune response of graft rejection in organ transplantation.
Zwirner
N W
NW
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8886, USA.
Dole
K
K
Stastny
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D011817:Rabbits
D015395:Histocompatibility Antigens Class I; D007106:Immune Sera; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D010455:Peptides