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Human lymphocyte function-associated antigens.

A M Krensky, F Sanchez-Madrid, T A Springer

    Survey of Immunologic Research
    |January 1, 1984
    PubMed
    Summary
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    Researchers identified three cell surface molecules (LFA-1, LFA-2, LFA-3) crucial for T cell immune responses. These molecules play roles in cell adhesion and cytolysis, offering potential diagnostic and therapeutic applications.

    Area of Science:

    • Immunology
    • Cell Biology
    • Molecular Biology

    Background:

    • Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells mediate crucial immune responses.
    • Understanding the molecular interactions governing CTL-target cell conjugates is essential for immune function.
    • Previous studies have identified various molecules involved in cell-mediated cytotoxicity.

    Purpose of the Study:

    • To identify and characterize novel cell surface molecules involved in T cell-mediated cytolysis and other immune functions.
    • To investigate the roles of these molecules in T cell interactions, including adhesion and antigen recognition.
    • To explore the potential diagnostic and therapeutic relevance of these molecules in immune responses.

    Main Methods:

    • Generation of monoclonal antibodies (mAbs) that block cytolysis mediated by a specific CTL line.

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  • Utilized these mAbs to identify and define cell surface molecules, designated LFA-1, LFA-2, and LFA-3.
  • Assessed the functional impact of anti-LFA mAbs on various immune cell functions, including CTL-mediated cytolysis, NK-mediated cytolysis, and T cell proliferation.

    • Main Results:

    • Identified three distinct cell surface molecules: LFA-1, LFA-2, and LFA-3, using blocking mAbs.
    • Demonstrated that anti-LFA mAbs inhibit all studied CTL and proliferative functions.
    • Showed that anti-LFA-1 mAbs inhibit NK-mediated cytolysis, suggesting a role in adhesion.
    • LFA-2 appears to be a T cell function-specific molecule, potentially involved in antigen recognition or non-specific interactions.
    • Anti-LFA-3 mAbs bind to target cells, indicating LFA-3 may be a ligand for an effector-specific receptor.

    Conclusions:

    • The identified LFA antigens (LFA-1, LFA-2, LFA-3) highlight the molecular complexity of CTL-target interactions.
    • Human LFA-1 may be involved in the crucial cell adhesion step of immune cell interactions.
    • LFA-2 is a T cell function-specific molecule, with its precise role in antigen recognition or adhesion still under investigation.
    • LFA-3 may serve as a target ligand for effector cell receptors, contributing to specific immune recognition.
    • Anti-LFA monoclonal antibodies are valuable tools for studying the T cell immune response and hold promise for clinical applications.