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BMC Immunol. 2009 Sep 22;10:51. doi: 10.1186/1471-2172-10-51.

Biochemical analysis of CTLA-4 immunoreactive material from human blood.

Author information

1
Aurora St Luke's Medical Center, Transplant Research Lab, Milwaukee, WI 53215, USA. matt.tector@aurora.org

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.

PMID:
19772653
PMCID:
PMC2758829
DOI:
10.1186/1471-2172-10-51
[Indexed for MEDLINE]
Free PMC Article

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