1. Biochemical analysis of CTLA-4 immunoreactive material from human blood.
- Author
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Tector M, Khatri BO, Kozinski K, Dennert K, and Oaks MK
- Subjects
- Antibodies, Monoclonal immunology, Antigen-Antibody Complex blood, Antigen-Antibody Complex chemistry, Antigens, CD blood, Antigens, CD chemistry, Antigens, CD immunology, B7-1 Antigen immunology, B7-1 Antigen metabolism, B7-2 Antigen immunology, B7-2 Antigen metabolism, Blood Proteins chemistry, Blood Proteins immunology, CTLA-4 Antigen, Chemical Fractionation, Humans, Immunomodulation, Mass Spectrometry, Myasthenia Gravis blood, Protein Binding, Antigen-Antibody Complex immunology, Antigens, CD metabolism, Blood Proteins metabolism, Myasthenia Gravis immunology
- Abstract
Background: CTLA-4 was initially described as a membrane-bound molecule that inhibited lymphocyte activation by interacting with B7.1 and B7.2 molecules on antigen presenting cells. Alternative splicing of mRNA encoding the CTLA-4 receptor leads to the production of a molecule (sCTLA-4) that lacks a membrane anchor and is therefore secreted into the extracellular space. Despite studies finding that people with autoimmune disease more frequently express high levels of sCTLA-4 in their blood than apparently healthy people, the significance of these findings is unclear., Methods: Molecules isolated from blood using CTLA-4 specific antibodies were analyzed with ligand binding assays, mass spectroscopy, and biochemical fractionation in an effort to increase our understanding of CTLA-4 immunoreactive material., Results: Mass spectroscopy analysis of the molecules recognized by multiple CTLA-4-specific antibodies failed to identify any CTLA-4 protein. Even though these molecules bind to the CTLA-4 receptors B7.1 and B7.2, they also exhibit properties common to immunoglobulins., Conclusion: We have identified molecules in blood that are recognized by CTLA-4 specific antibodies but also exhibit properties of immunoglobulins. Our data indicates that what has been called sCTLA-4 is not a direct product of the CTLA-4 gene, and that the CTLA-4 protein is not part of this molecule. These results may explain why the relationship of sCTLA-4 to immune system activity has been difficult to elucidate.
- Published
- 2009
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