Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets

Abstract

We have identified and biochemically characterized an antigen, 8A3, which is expressed on activated T lymphoblasts and activated platelets. Monoclonal antibodies to 8A3 were raised against the primitive lymphoid/myeloid cell line KG1a and additionally bound to the erythroleukemia-derived cell line HEL, whilst exhibiting little or no reactivity with a panel of other hematopoietic cell lines. The 8A3 antigen was expressed on poorly differentiated T-cell leukemias and on phytohemagglutinin-activated T-cells maintained in interleukin-2 (7,000 sites/cell). This antigen, though not detected on resting platelets, was expressed on thrombin-activated platelets (2,000 sites/platelet). Antibodies to 8A3 identified polypeptides of Mr 170,000 and 150,000 in lysates of surface-iodinated KG1a cells, T lymphoblasts, and activated platelets under both reducing and nonreducing conditions. However, peptide mapping and susceptibily to glycosidases indicated that the 8A3 antigen was a monomeric glycoprotein of Mr 170,000 which contained two N-linked endoglycosidase H-sensitive glycans, and that the Mr 150,000 structure was derived from it by proteolytic degradation. The 8A3 antigen was not detectably phosphorylated in KG1a cells in vivo, nor did immune complexes containing it exhibit kinase activity in vitro. Structural and serologic characteristics of the 8A3 antigen indicate that it is different from other previously described leukocyte activation antigens including transferrin receptors, interleukin-2 receptors, members of the integrin family of adhesion molecules, or “restricted” members of the leukocyte-common antigen/CD45 cluster. Furthermore, the 8A3 antigen does not appear to be related to the other previously described activation-specific platelet molecule, GMP140/PADGEM. This antibody may be useful in monitoring T-cell activation status in some clinical situations and in characterizing clinically relevant activation-associated platelet membrane alterations.

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA‐5 alloantigens

“…These contradictory results are either explained by the use of different CD109 mAbs or by differences in platelet preparation and buffers used. The mAbs 1B3 and 8A3 do not react with resting platelets but, in both cases, platelets were obtained by gel filtration in the presence of inhibitors of activation such as prostaglandin I 2 and acetylsalicylic acid (Sutherland et al, 1991;Bordin et al, 1997). Previous studies with mAb D2 showed binding to platelets obtained from standard platelet concentrates (Haregewoin et al, 1994), and this is confirmed in the current study.…”

Up‐regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity

“…(15) CD109-positive immunoreactivity in normal tissues was also detected in restricted cells, such as myoepithelial cells of the mammary, salivary and lacrimal glands, and basal cells of the prostate. (16) Our findings, together with previous reports showing CD109 expression on hematopoietic and mesenchymal stem cell subsets, activated T lymphoblasts and platelets, and some human tumor cell lines, (1,2,4,5) demonstrate that CD109 plays a role in cell proliferation and tumor development, especially that of SCC, and that CD109 expression in normal tissues may be strictly controlled. In the present study, we assessed the significance of CD109 expression in tumor development and cell proliferation using human oral tumor tissues and cancer cell lines.…”

Identification of CD109 as part of the TGF‐β receptor system in human keratinocytes

“…Although CD109 has been shown to be an activation antigen for T cells and platelets (24), to carry the platelet Gov alloantigen system (27), and to be expressed widely in human tissues (29), the physiological function of this protein is not known. Results from the present study linking CD109 function to regulation of TGF-␤1 signaling in vitro suggest that it may play a similar role in vivo.…”

“…CD109 is a GPI-anchored protein, first identified using monoclonal antibodies raised against the human leukemia cell line KG1a, on activated T cells and platelets and on a subset of hematopoetic progenitor cells (23,24), with a wider distribution reported more recently (25,26). Although CD109 has been found to represent the Gov alloantigen on platelets (27), and its molecular cloning as a novel member of the ␣2macroglobulin(␣2M)/complement gene family has recently been reported (28,29), its function has remained unknown.…”