Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocyte-common antigen (CD45).
The leukocyte common antigen (LCA) is a protein tyrosine phosphatase and is identified by the CD45 cluster of monoclonal antibodies. CD45 is expressed in high-density on cells of hematopoietic lineage and generally is immunoprecipitated as 4 bands (220, 205, 190, and 180 KDa). Genetic studies have shown that a single gene produces additional forms of the molecule by alternate splicing including CD45RA (220, 205), CD45RO (180), and CD45RB (220, 205, 190). We have prepared a CD45RB Mab termed "MT3" that binds to a sialic acid dependent epitope. Since the LCA is one of the major targets of antilymphocyte globulin, we assessed a panel of CD45 and CD45R Mab for their ability to inhibit alloreactivity in vitro. MT3 (CD45RB) inhibits the allogeneic MLR and inhibits CD4+ T cells from expressing interleukin 2 receptors, and prevents CD4+ CD45RA- T cells from entering the proliferative phase of the cell cycle. Mem 93 (CD45RA) inhibits the generation of cytotoxic T cells. These data suggest that the CD45RB and CD45RA isoforms of the LCA may be appropriate targets for in vivo immunotherapy.
John P. Robarts Research Institute, University Hospital, London, Ontario, Canada.
A I
AI
Lazarovits
S
S
Poppema
M J
MJ
White
J
J
Karsh
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure; D002453:Cell Cycle; D003429:Cross Reactions / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens