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Activation of LFA-1 through a Ca2(+)-dependent epitope stimulates lymphocyte adhesion

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Abstract

The leukocyte function-associated molecule-1 (LFA-1) plays a key role in cell adhesion processes between cells of the immune system. We investigated the mechanism that may regulate LFA-1-ligand interactions, which result in cell-cell adhesion. To this end we employed an intriguing anti-LFA-1 alpha mAb (NKI-L16), capable of inducing rather than inhibiting cell adhesion. Aggregation induced by NKI-L16 or Fab fragments thereof is not the result of signals transmitted through LFA- 1. The antibody was found to recognize a unique Ca2(+)-dependent activation epitope of LFA-1, which is essentially absent on resting lymphocytes, but becomes induced upon in vitro culture. Expression of this epitope correlates well with the capacity of cells to rapidly aggregate upon stimulation by PMA or through the TCR/CD3 complex, indicating that expression of the NKI-L16 epitope is essential for LFA- 1 to mediate adhesion. However, expression of the NKI-L16 epitope in itself is not sufficient for cell binding since cloned T lymphocytes express the NKI-L16 epitope constitutively at high levels, but do not aggregate spontaneously. Based on these observations we propose the existence of three distinct forms of LFA-1: (a) an inactive form, which does not, or only partially exposes the NKI-L16 epitope, found on resting cells; (b) an intermediate, NKI-L16+ form, expressed by mature or previously activated cells; and (c) an active (NKI-L16+) form of LFA- 1, capable of high affinity ligand binding, obtained after specific triggering of a lymphocyte through the TCR/CD3 complex, by PMA, or by binding of NKI-L16 antibodies

Topics: Articles
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2288821
Provided by: PubMed Central
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    1. (1988). A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18
    2. (1987). Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3).
    3. (1987). Aggregation of complement receptors on human neutrophils in the absence of ligand.
    4. (1987). cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein p150,95.
    5. (1989). Constitutive and stimulusinduced phosphorylation of CD 11/CD18 leukocyte adhesion molecules.
    6. (1986). Cross-linking of surface Immunoglobulin on B lymphocytes induces both intracellular Ca 2+ release and Ca ~+ influx: analysis with indo-1.
    7. (1986). de Vries.
    8. Induction of aggregation and enhancement of proliferation and IL-2 secretion in human T cells by antibodies to CD43.
    9. (1988). Lymphocyte Function-associated Antigen (LFA- 1 ) interaction with Intercellular Adhesion Molecule- 1 (ICAM- 1 ) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells.
    10. (1989). Phorbol ester modulation of integrinmediated cell adhesion: a postreceptor event.
    11. (1988). Phosphorylation oft cell membrane proteins by activators of protein kinase
    12. (1989). Regulated expression ofMg 2+ binding epitope on leukocyte integrin ยข subunits.
    13. (1989). T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature (Lond.).
    14. (1988). Triggering of co-mitogenic signals in T cell proliferation by anti-LFA-1 (CD18, CD1 la), LFA-3, and CD7 monoclonal antibodies.
    15. (1988). Triggering of T cetl proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes.

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