Abstract
CTLA-4 is an immunoregulatory receptor expressed on the surface of activated T and B lymphocytes. The counterreceptors for CTLA-4 are the B7 family molecules. We describe alternatively spliced mRNAs expressed in hematolymphoid tissues of humans, mice, and rats that lack the transmembrane domain coded by exon 3 of the CTLA-4 gene. These alternate transcripts were detected by RT-PCR in B cells and resting T cells of both the CD4 and the CD8 phenotype. Activation of human blood mononuclear cells with PHA or anti-CD3 + anti-CD28 monoclonal antibodies appears to effect a decrease in the amount of the alternative transcript relative to the full-length transcript. Recombinant sCTLA-4 is a B7-binding protein and has immunomodulatory effects as measured by inhibition of the mixed leukocyte response. Human serum contains immunoreactive material consistent with a native soluble form of CTLA-4.
Copyright 2000 Academic Press.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Abatacept
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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Antigens, CD
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Antigens, Differentiation / blood
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Antigens, Differentiation / genetics*
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B7-1 Antigen
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B7-2 Antigen
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Base Sequence
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CTLA-4 Antigen
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Cloning, Molecular
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Female
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Hematopoietic Stem Cells / immunology
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Humans
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Immunoconjugates*
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Lymphoid Tissue / immunology
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Membrane Glycoproteins
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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RNA, Messenger / isolation & purification
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Rats
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Receptors, Immunologic / blood
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Receptors, Immunologic / genetics*
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Solubility
Substances
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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CD86 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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Cd86 protein, mouse
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Cd86 protein, rat
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Ctla4 protein, mouse
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Ctla4 protein, rat
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Immunoconjugates
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Membrane Glycoproteins
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Membrane Proteins
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RNA, Messenger
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Receptors, Immunologic
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Abatacept
Associated data
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GENBANK/AF012711
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GENBANK/AF012712
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GENBANK/AF012713
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GENBANK/U90270
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GENBANK/U90271
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GENBANK/U90273