Characterization and localization of the Gova/b alloantigens to the glycosylphosphatidylinositol-anchored protein CDw109 on human platelets

Abstract

The Gova/b alloantigens are expressed on a 175-kD protein (GP175) on human platelets. Anti-Gov alloantibodies have been implicated in posttransfusion purpura and alloimmune neonatal thrombocytopenia. In this report we characterize the immunochemistry of the alloantigens and identify the platelet protein that expresses the Gov epitopes. Approximately 50% of GP175 containing the Gov epitope was released from platelets treated with phosphatidylinositol-specific phospholipase C, indicating that at least some of this protein exists as a glycosylphosphatidylinositol (GPI)-linked isoform. Radioimmunoprecipitation and immunodepletion studies indicated that the Gova/b alloantigens are expressed on the GPI-anchored CDw109 protein. The Gova/b epitopes were expressed on an extracellular, 120-kD soluble fragment (p120) of CDw109 produced by calcium-dependent protease cleavage. Anti-Gov immunoprecipitates of chymotryptic digests of p120 contained 70- and 52-kD fragments of CDw109. Deglycosylation of native CDw109 had no effect on recognition by Gov alloantisera; however, the epitopes were destroyed after exposure to sodium dodecyl sulfate. Gova/b alloantigens were expressed on platelets and PHA-activated T-cells, cultured human umbilical vein endothelial cells, and by many different tumor cell lines, consistent with the tissue distribution of CDw109.

Frequencies of maternal platelet alloantibodies and autoantibodies in suspected fetal/neonatal alloimmune thrombocytopenia, with emphasis on human platelet antigen‐15 alloimmunization

“…[4] described a new alloantigen system, the Gov a/b system, that they discovered in association with transfusion incompatibilities and later on in association with FNAITP [5]. These authors localized this alloantigen to CD109 [6]. The molecular characterization of the Gov system [7] facilitated the genotyping of large cohorts and definition of the gene frequency among these individuals, which was found to be similar to that seen by serological investigation on the initially small number of individuals [4].…”

Relevance of the HPA‐15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes

“…Primary structure analysis showed that CD109 is a novel member of the α2‐macroglobulin–C3, C4, and C5 family of thioester‐containing proteins 10 . The function of CD109 is not yet known, however 11,12 . In view of the putative complement‐like spatially restricted thioester reactivity and its location as GPI‐linked cell surface molecule, CD109 might function as membrane‐bound cross‐linking reagent, thereby mediating cell‐cell interactions that might play a role in hematopoiesis and primary hemostasis 10 …”

Gene frequencies of the HPA‐15 (Gov) platelet alloantigen system in Brazilians

“…The HPA‐15 (Gov) alloantigen system is carried on the protein CD109, a glycosylphosphatidylinositol‐linked glycoprotein of approximately 170 Kd, member of the α2 macroglobulin/C3, C4, C5 family of thioester‐containing proteins (Smith et al ., 1995; Lin et al ., 2002). It is found on a subset of haematopoietic stem and progenitor cells and on activated platelets and T cells.…”