INHIBITION OF T-CELL MITOGENESIS BY A NOVEL ANTI-CD45R MONOCLONAL-ANTIBODY

CD45 consists of a major family of membrane glycoproteins which have p rotein tyrosine phosphatase activity and regulate early activation eve nts, progression and maturation signals in leucocytes. Various isoform s of CD45 (M(r) 180-240 kDa) regulate sets of intermolecular associati ons between different surface receptors, and appear to be differential ly expressed on B and T cells (namely CD45RA, B or CD45RO). We describ e a novel IgG2a mAb directed against restricted and unique CD45R modif ied epitopes expressed preferentially on peripheral blood T cells. Thi s anti-CD45R antibody (I(2)4c) at concentrations of 50 and 200 ng/mL i nhibited mitogenic T cell lectin and anti-CD3-stimulated lymphocyte pr oliferation and blocked associated IL-2 secretion in vitro. Phorbol es ter-stimulated mitogenesis was unaltered suggesting that the inhibitio n occurs independent of protein kinase C-mediated pathways, Western bl otting and immunoprecipitation 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 proteo lytic fragment was recognized. I(2)4c may inhibit T cell mitogenesis b y direct effects on CD45R alone or by preventing interaction with othe r membrane-associated proteins and hence adhesive interactions with mo nocytes, Such interactions may however inhibit the initiation of signa l transduction and, as a consequence, alter cellular activation by mit ogenic lectins and anti-CD3 in vitro.