Distribution and modulation of a human leukemia-associated antigen (CALLA).
CALLA is a 100,000-dalton surface glycoprotein expressed by malignant cells of patients with clinically important subtypes of acute leukemia. Incubation of human leukemic cells expressing CALLA with specific monoclonal antibody (J5) at 37 degrees C causes rapid and selective internalization and degradation of this antigen (antigenic modulation). In these studies we show that CALLA-specific monoclonal antibodies also identify a cell surface glycoprotein having a m. w. of approximately 100,000 on 2 to 6% of nonmyeloid nucleated cells of normal adult bone marrow, on normal fibroblasts in tissue culture, and on cells of several nonhematopoietic human tumor cell lines. J5 antibody similarly modulates the surface expression of CALLA on nonleukemic cell populations, although the extent of modulation at a given concentration of antibody varied considerably. Modulation was almost complete for CALLA on cells of normal bone marrow, but was highly variable for cells of nonhematopoietic cell lines, possibly reflecting variability in antibody access to surface antigen. Using fluoresceinated or iodinated J5 antibody to modulate expression of CALLA on cells of leukemic cell lines, we show that antibody-antigen complexes undergo a temperature-dependent redistribution on the cell surface during modulation to form microaggregates. Antibody as well as antigen is then internalized. Studies of [35S]methionine-labeled cells indicate that synthesis of CALLA continues despite modulation of its surface expression by specific antibody, implying that the presence of CALLA on the cell surface reflects a dynamic equilibrium between the processes of surface expression of newly synthesized glycoprotein and its spontaneous and antibody-mediated clearance. The implications of these observations for immunotherapy are discussed.
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D001666:Binding Sites, Antibody; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000276:immunology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D015260:Neprilysin
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008565:Membrane Proteins; D015260:Neprilysin