A direct measurement of the avidity of the junction between a cytotoxic T lymphocyte and its target cell was achieved by using a biophysical approach. A micromanipulation technique was used to determine the force required to separate a cytotoxic T cell (human clone F1, with specificity for HLA-DRw6) from its specific target cell (JY: HLA-A2, -B7, -DR4, w6) prior to delivery of the lethal hit. The force required to separate the F1-JY pair is 1.5 X 10(4) dynes per square centimeter. This junction avidity for F1-JY pairs is 6 to 13 times greater than that for F1-F1 and JY-JY pairs; the F1-JY conjugate requires a stronger separating force and is more easily rejoined than the homologous cell pairs. This study provides an estimate of the avidity of cytotoxic T cells for their target cells and insights into the biophysical correlates of the molecular complexes formed in the interaction of cytotoxic T cells and their targets during the cytotoxic process.
It has been well established that T lymphocytes can be triggered by antigen interacting with the T cell antigen receptor (TcR)' or by antibodies binding to the associated structure CD3 . Recent findings (1) suggest the existence of alternative pathways of T lymphocyte activation. Certain mAbs to the cell surface molecule CD2 (T11, LFA-2) activate T lymphocytes. T lymphocyte activation is dependent on the epitope recognized by the anti-CD2 mAb. mAbs to a number of other surface antigens provide a costimulatory signal . mAbs to CD5 (Tp67) (2) and CDw28 (Tp44) (3) augment T lymphocyte proliferation and IL-2 production. In the presence of PMA, mAbs to Tp44 stimulate purified T lymphocytes directly (3). We report here that an mAb to the surface protein sialophorin stimulates T lymphocyte proliferation in a manner similar to mAbs to CD3 and CD2 .Sialophorin, previously called gpL 115, was found to be deficient in quantity and/or defective in lymphocytes of patients with the X-linked immunodeficiency Wiskott-Aldrich syndrome (4-6) . A molecule indistinguishable from sialophorin of normal lymphocytes was purified to homogeneity from cells of the lymphoblastoid cell line CEM (6, 7). Sialophorin of CEM cells consists of >50% carbohydrate, primarily -100 0-linked units of sialic acid, galactose, and galactosamine, and a single -520-amino-acid polypeptide chain rich in serine, threonine, and proline (7,8).In this report, the mAb L10 which recognizes a surface epitope of sialophorin (6) was used to investigate the expression and the function of the molecule . Fluorescent staining with mAb indicated that sialophorin is expressed on all cells in the thymus and on a fraction of bone marrow and peripheral blood cells. Functional studies demonstrate that L 10 mAb triggers the proliferation of
Human monocyte adhesion to vascular endothelium is an important transitional event in mononuclear phagocyte development. The molecular mechanism involved in monocyte adhesion to endothelial cells was studied using purified human monocytes and a panel of monoclonal antibodies (MAb). The purified human monocytes were phenotypically characterized and expressed relatively low levels of HLA class II antigens. The monocytes were labeled with Indium-111 to provide high specific activity and a sensitive measure of adhesion. Using this radionuclide adhesion assay, monocytes demonstrated consistent and reproducible adhesion to a confluent monolayer of human umbilical vein-derived endothelial cells. To identify the cell surface molecules involved in human monocyte-endothelial cell adhesion, 15 MAb to 11 monocyte surface structures were used to attempt to inhibit adhesion. MAb recognizing 10 monocyte cell surface molecules did not inhibit adhesion. In contrast, MAb recognizing the alpha and beta subunits of LFA-1 (lymphocyte function-associated) significantly inhibited monocyte adhesion to endothelial cells. Monocyte adhesion was comparably inhibited by F(ab')2 and intact MAb. Significant inhibition was observed at 5 micrograms/ml of anti-LFA-1 MAb. These results indicate that the alpha and beta subunits of the LFA-1 membrane molecule are involved in human monocyte-endothelial cell adhesions.
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