Abstract
CTLA4 ligands are important costimulatory molecules because soluble CTLA4Ig blocks the induction of T cell responses and induces T cell tolerance. As CTLA4 immunoglobulin (CTLA4Ig) binds B7 when the latter is expressed on fibroblasts, it was widely assumed that CTLA4Ig blocks T cell costimulation by blocking the function of B7. Here we show that the major costimulatory ligand bound by CTLA4Ig (which we term CTLA4 ligand A) on antigen-presenting cells are not encoded by the B7 gene. CTLA4 ligand A also differs from B7 in cellular distribution and in the respective levels of expression. Both B7 and CTLA4 ligand A are critically involved in T cell costimulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abatacept
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Animals
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Antibodies, Monoclonal
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Antigen-Presenting Cells / immunology*
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Antigens, CD
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Antigens, Differentiation / immunology*
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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Base Sequence
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CD4 Antigens / immunology
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CTLA-4 Antigen
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Cricetinae
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DNA Primers
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Flow Cytometry
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HLA-B7 Antigen / biosynthesis*
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HLA-B7 Antigen / immunology*
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Immunoconjugates*
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation*
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Mice
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Mice, Inbred CBA
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Molecular Sequence Data
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Polymerase Chain Reaction / methods
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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T-Lymphocytes / immunology*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CD4 Antigens
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CTLA-4 Antigen
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Ctla4 protein, mouse
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DNA Primers
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HLA-B7 Antigen
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Immunoconjugates
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Lipopolysaccharides
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RNA, Messenger
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Abatacept