MICA antigens are polymorphic glycoproteins expressed on the surface of human endothelial cells and other cells. Antibodies against MICA have been found in transplant recipients and were found to be associated with decreased survival of kidney allografts. In the present work, we investigated the polymorphisms that are recognized by antibodies against MICA. Soluble MICA recombinant proteins representing 11 common alleles, two hybrid alleles, and two single amino acid mutated alleles were produced. Patterns of reactivity were determined with MICA bound to Luminex beads. In some studies, sera containing antibodies against MICA were absorbed by cell lines transfected with MICA*001, MICA*002, MICA*008, and MICA*009 or with untransfected cells, followed by testing of antibody reactivity against MICA proteins bound to beads. The monoclonal antibodies and sera used in this study were found to recognize up to 14 distinct MICA epitopes as demonstrated by their differential absorption/reactivity patterns. Among these, nine epitopes correlated with a single unique amino acid: one shared two signature amino acids, one shared three signature amino acids in close proximity, and three epitopes involved multiple amino acids in a nonlinear sequence. Two groups of public epitopes (MICA-G1 and MICA-G2) were characterized. MICA shared epitopes were determined by reactivity loss in single MICA antigen bead assays by absorption with MICA transfectants. Since these epitopes may be targets for antibody binding and possibly antibody-mediated allograft rejection, epitope identification may help understand the development of MICA antibodies and to identify suitable donors for sensitized transplant recipients.

Objective Central renin–angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined. Results Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT1R and AT2R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT1aR and AT2R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT1R protein and AT1aR mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT2R mRNA and protein were increased only in males. Prenatal dehydration resulted in a significant increase in intracerebroventricular angiotensin II-induced water intake in male, but not female, offspring. Conclusion The results provided new information that antenatal water deprivation induces a reprogramming of brain RAS and Ang II receptor expression patterns and alters the central Ang II-mediated dipsogenic response in offspring in a sex-dependent manner.

The major histocompatibility complex (MHC) encodes the HLA class I antigens expressed on the surface of most nucleated cells and the HLA class II antigens which are expressed mostly in B lymphocytes, monocytes and dendritic cells. Mismatched HLA antigens are the main source of the immune response that leads to the rejection of allografts. In some patients however, rejection may occur without a detectable response to donor HLA antigens. We have been interested in characterizing antibodies that develop in transplant recipients who do not appear to have antibodies against HLA. For this purpose, we focused our attention to antigens which are expressed on the surface of endothelial cells and are not found on peripheral blood lymphocytes. These include the MICA and MICB antigens, which are encoded by loci in the MHC; certain autoantigens expressed on the endothelium; and a family of polymorphic antigens expressed on endothelial cells which are distinct from HLA and elicit production of antibodies that appear also to be associated with graft failure. Antibodies against MICA have been associated with allograft rejection. MICB antibodies are only rarely found. The autoantibodies and the endothelial specific alloantibodies are being characterized in ongoing studies.

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