Inhibition of T cell mitogenesis by a novel anti-CD45R monoclonal antibody.
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 (Mr 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 (I(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 immunoprecipitation of purified cell lysates reveals that I(2)4c preferentially binds the higher Mr 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.
Robson
S C
SC
Department of Surgery, Harvard University, Boston, MA, USA.
Siegel
J B
JB
Kirsch
R E
RE
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D008565:Membrane Proteins; D017493:Leukocyte Common Antigens