Abstract
BackgroundCTLA-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.MethodsMolecules 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.ResultsMass 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.ConclusionWe 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.
Highlights
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
CTLA-4-TM is a co-receptor for the B7.1 (CD80) and B7.2 (CD86) molecules expressed on antigen presenting cells [4,5]
Our results suggest that the immunoreactive material in human blood is not the direct product of the sCTLA-4 alternate transcript and has several biochemical features of human immunoglobulin
Summary
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. BMC Immunology 2009, 10:51 http://www.biomedcentral.com/1471-2172/10/51 cal synapse [10], increases tryptophan catabolism by antigen presenting cells [11,12] and binds B7.1 and B7.2 preventing activation of lymphocytes through the costimulatory lymphocyte receptor CD28 [13]. Another transcript of the CTLA-4 gene encodes a molecule lacking the transmembrane domain, producing a soluble CTLA4 polypeptide referred to as sCTLA-4 [14,15]. The molecule does not bind the B7 family ligands [19] and has been referred to as ligand-independent CTLA-4 (liCTLA-4)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
