Low affinity of cell surface lymphocyte function-associated antigen-1 (LFA-1) generates selectivity for cell-cell...

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Lymphocyte function-associated antigen-1 (LFA-1) is a key immune cell receptor involved in T cell activation and adhesion.
• Intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1, mediating cell-cell interactions.
• The affinity of LFA-1 for ICAM-1 is regulated by 'inside-out' signaling, influencing immune cell responses.

Purpose of the Study:

• To investigate the binding characteristics of LFA-1 on activated T cells to ICAM-1 in different formats (soluble dimers vs. coated particles).
• To determine the influence of particle size on T cell adhesion to ICAM-1.
• To elucidate the role of LFA-1 affinity states in mediating selective binding to ICAM-1-bearing surfaces.

Main Methods:

• Utilized activated T cells and varying concentrations of soluble ICAM-1 dimers.
• Employed ICAM-1-coated particles of different sizes (0.5 µm to larger) to assess binding.
• Investigated LFA-1 affinity modulation using activating antibodies.

Main Results:

• Activated T cells exhibited low-affinity binding to soluble ICAM-1 dimers but avid binding to ICAM-1-coated surfaces.
• A size-dependent binding threshold was observed: T cells adhered to particles ≥1 µm but not <0.5 µm.
• LFA-1 binding to all ICAM-1 forms occurred when LFA-1 was converted to a high-affinity state via activating antibodies.

Conclusions:

• The selective binding of activated T cells to cell-sized particles is attributed to LFA-1 maintaining a low-affinity state on the T cell surface.
• Physiological conditions generate high-affinity LFA-1 through initial low-affinity interactions with ICAM-1.
• These findings redefine the understanding of LFA-1 inside-out signaling and its role in immune cell adhesion selectivity.