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Inhibition of T cell mitogenesis by a novel anti‐CD45R monoclonal antibody
Author(s) -
ROBSON SIMON C,
SIEGEL JONATHAN B,
KIRSCH RALPH E
Publication year - 1996
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1996.9
Subject(s) - biology , microbiology and biotechnology , t cell , il 2 receptor , t lymphocyte , epitope , monoclonal antibody , cell surface receptor , in vitro , receptor , antibody , biochemistry , cytotoxic t cell , immunology , immune system
Summary CD45 consists of a major family of membrane glycoproteins which have protein tyrosine phosphatase activity and regulate early activation events, progression and maturation signals in leucocytes. Various isoforms of CD45 (M r 180–240 kDa) regulate sets of intermolecular associations between different surface receptors, and appear to be differentially expressed on B and T cells (namely CD45RA, B or CD45RO). We describe a novel IgG2a mAb directed against restricted and unique CD45R modified epitopes expressed preferentially on peripheral blood T cells. This anti‐CD45R antibody (l(2)4c) at concentrations of 50 and 200 ng/mL inhibited mitogenic T cell lectin and anti‐CD3‐stimulated lymphocyte proliferation and blocked associated IL‐2 secretion in vitro. Phorbol ester‐stimulated mitogenesis was unaltered suggesting that the inhibition occurs independent of protein kinase C‐mediated pathways. Western blotting and immuno‐precipitation of purified cell lysates reveals that I(2)4c preferentially binds the higher M r , bands of CD45 expressed on T cells. Following T cell activation in vitro , the 190 kDa band became more predominant and an additional 130 kDa protein, possibly a proteolytic fragment was recognized. I(2)4c may inhibit T cell mitogenesis by direct effects on CD45R alone or by preventing interaction with other membrane‐associated proteins and hence adhesive interactions with monocytes. Such interactions may however inhibit the initiation of signal transduction and., as a consequence, alter cellular activation by mitogenic lectins and anti‐CD3 in vitro.