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Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but aspects of its molecular nature remain undefined. In particular, the characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an alternatively spliced mRNA of CTLA4 lacking transmembrane-encoding exon 3 has been hindered by the difficulty in distinguishing it from the transmembrane isoform of CTLA-4, Tm-CTLA-4. In the current study, sCTLA-4 has been analyzed using novel mAbs and polyclonal Abs specific for its unique C-terminal amino acid sequence. We demonstrate that the sCTLA-4 protein is secreted at low levels following the activation of primary human CD4(+) T cells and is increased only rarely in the serum of autoimmune patients. Unexpectedly, during our studies aimed to define the kinetics of sCTLA-4 produced by activated human CD4(+) T cells, we discovered that Tm-CTLA-4 is associated with microvesicles produced by the activated cells. The functional roles of sCTLA-4 and microvesicle-associated Tm-CTLA-4 warrant further investigation, especially as they relate to the multiple mechanisms of action described for the more commonly studied cell-associated Tm-CTLA-4.

Original publication




Journal article


J Immunol

Publication Date





889 - 900


Adult, Animals, Antibodies, Monoclonal, Antibody Specificity, Blotting, Western, CD4-Positive T-Lymphocytes, CTLA-4 Antigen, Cells, Cultured, Cytoplasmic Vesicles, Diabetes Mellitus, Type 1, Female, Graves Disease, HeLa Cells, Humans, Immunoassay, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Microscopy, Immunoelectron, Middle Aged, Protein Isoforms, Solubility, Young Adult