Monoclonal antibodies against leucoagglutinin-reactive human T-lymphocyte surface components. II. Studies on the mechanism of K46M-induced activation and determination of the frequency of responding cells.
A monoclonal antibody, K46M (IgM kappa), obtained after immunization with leucoagglutinin (La)-reactive T-cell surface components, stimulated human lymphocytes to proliferate. It induced maximal proliferation at greater than 20 micrograms IgM/ml after 3-4 days of culture. Cells stimulated by K46M produced interleukin 2 (IL-2) and gamma interferon (IFN-gamma) and expressed receptors for IL-2 and transferrin. The majority of the activated cells were phenotypically T cells as defined by monoclonal antibodies against CD3 and CD2, and an increase in the K46M-positive cells was also observed during the activation period. K46M-activated cells display major histocompatibility complex (MHC)-unrestricted cytotoxicity against several cultured target cells. The frequencies of the cytotoxic and of the proliferative precursor cells were determined using a limiting dilution assay. K46M seems to activate a larger fraction of cytotoxic precursor cells against Molt 4 than against K562, but the statistical significance of these observations requires further exploration. Both K46M or La activated 40% of PBL to proliferate, whereas 70% of PBL were induced by OKT3. However, the frequency of K46M-activated cells was 40% only when the lymphocytes were plated at low cell densities, i.e. less than 0.5 cells per well. At higher densities an inhibition of proliferation was seen that resulted in a biphasic response curve, indicating that the activation of PBL by K46M was not a single hit event. This was not found with either La or OKT3. Whether K46M, in contrast to OKT3 and La, activates a subpopulation with suppressor activity remains to be established.
Berzins
T
T
Department of Immunology, University of Stockholm, Sweden.
Vargas-Cortes
M
M
Hammarström
M L
ML
Larsson
A
A
Aguilar-Santelises
M
M
Andersson
G
G
Hammarström
S
S
Perlmann
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D007887:Fabaceae; D006801:Humans; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens / Q000502:physiology; D010835:Phytohemagglutinins / Q000276:immunology*; D037121:Plant Lectins; D010946:Plants, Medicinal; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D008934:Mitogens; D010835:Phytohemagglutinins; D037121:Plant Lectins; C100156:leukoagglutinins, plants