Abstract
A novel 75 kDa membrane protein, TIRC7, is described that exhibits a central role in T cell activation in vitro and in vivo. Modulation of TIRC7-mediated signals with specific anti-TIRC7 antibodies in vitro efficiently prevents human T cell proliferation and IL-2 secretion. Moreover, anti-TIRC7 antibodies specifically inhibit type 1 subset specific IFN-gamma expression but spare the type 2 cytokine IL-4. Diminished proliferation but not IFN-gamma secretion is reversible by exogenous rIL-2. An anti-TIRC7 antibody that cross-reacts with the 75 kDa rat homolog exhibits inhibition of rat alloimmune response in vitro and significantly prolongs kidney allograft survival in vivo. Targeting of TIRC7 may provide a novel therapeutic approach for modulation of the immune response.
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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Acute Disease
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Amino Acid Sequence
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Animals
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Antibodies
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Base Sequence
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DNA Primers / genetics
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DNA, Complementary / genetics
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Graft Rejection / immunology
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Graft Rejection / pathology
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Graft Rejection / prevention & control*
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Humans
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In Vitro Techniques
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Interleukin-2 / biosynthesis
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Kidney Transplantation / immunology
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Kidney Transplantation / pathology
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Lymphocyte Activation
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Male
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Molecular Sequence Data
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Molecular Weight
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Protein Subunits*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Lew
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Rats, Inbred WF
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Signal Transduction
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transplantation, Homologous
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Vacuolar Proton-Translocating ATPases*
Substances
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Antibodies
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DNA Primers
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DNA, Complementary
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Interleukin-2
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Membrane Proteins
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Protein Subunits
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RNA, Messenger
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TCIRG1 protein, human
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Vacuolar Proton-Translocating ATPases