Early lymphocyte activation molecule defined by the monoclonal antibody MLR-3: biochemical and functional studies.
The MLR-3 monoclonal antibody reacts with activated but not with resting lymphocytes. We report that MLR-3 identifies an early activation molecule since its binding is detectable on T cells 1.5-2 hr after in vitro activation. Its expression, therefore, does not require DNA synthesis and precedes, by many hours, that of the receptors for interleukin-2 (IL-2R) and transferrin (TF-R). The MLR-3 antigen is also found on activated thymocytes (including the large early thymic CD3- subset) and B cells. The majority of T- and B-lymphoblastoid cell lines, as well as the myeloid and erythroid cell lines HL60, GM1 and K562, are MLR-3+; conversely, non-haemopoietic cell lines are MLR-3 negative. Seventy percent of B-cell chronic lymphocytic leukaemia and 15% of B non-Hodgkin's lymphomas (B-NHL) are MLR-3+. On tissue sections MLR-3 is reactive with epithelia, sweat glands, hair follicles and Henle's loop but not with vessels, connective, endothelium and many other tissues. In vitro studies show that MLR-3 (1-100 micrograms/ml) significantly alters the thymidine uptake of mitogen-treated lymphocytes:augmentation is found when T and B cells are induced with TPA-Ionomycin and reduction when induced with phytohaemoagglutinin (PHA) or Staphylococcus aureus Cowan strain 1 (SAC), respectively. On SDS-PAGE, MLR-3 immunoprecipitates a disulphide-linked heterodimer of MW 29,000-35,000: both subunits are glycosylated, phosphorylated and exhibit a pI of 4.1 and 5.0, respectively. Our data, particularly the in vitro results, suggest that the MRL-3 molecule could have an important role in the early hours of activation for the progression of resting lymphocytes into mitosis.
Delia
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D
Division of Experimental Oncology A, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Traversari
C
C
Ballinari
D
D
Cattoretti
G
G
Fontanella
E
E
Polli
N
N
Della Porta
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis*; D002455:Cell Division; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D013755:Tetradecanoylphorbol Acetate