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CD2 molecules redistribute to the uropod during T cell scanning: implications for cellular activation and immune
Elena V Tibaldi1, Ravi Salgia, Ellis L Reinherz
1Laboratory of Immunobiology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Abstract:
Dynamic binding between CD2 and CD58 counter-receptors on opposing cells optimizes immune recognition through stabilization of cell-cell contact and juxtaposition of surface membranes at a distance suitable for T cell receptor-ligand interaction. Digitized time-lapse differential interference contrast and immunofluorescence microscopy on living cells now show that this binding also induces T cell polarization. Moreover, CD2 can facilitate motility of T cells along antigen-presenting cells via a movement referred to as scanning. Both activated CD4 and CD8 T cells are able to scan antigen-presenting cells surfaces in the absence of cognate antigen. Scanning is critically dependent on T cell beta-integrin function, as well as myosin light chain kinase. More importantly, surface CD2 molecules rapidly redistribute on interaction with a cellular substratum, resulting in a 100-fold greater CD2 density in the uropod versus the leading edge. In contrast, no redistribution is observed for CD11a/CD18 or CD45. Molecular compartmentalization of CD2, T cell receptor, and lipid rafts within the uropod prearranges the cellular activation machinery for subsequent immune recognition. This "presynapse" formation on primed T cells will likely facilitate the antigen-dependent recognition capability required for efficient immune surveillance.
Insights
Dynamic CD2-CD58 binding enhances T cell immune recognition by stabilizing cell contact and inducing T cell polarization. This interaction facilitates T cell scanning of antigen-presenting cells, optimizing immune surveillance.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Dynamic binding between CD2 and CD58 receptors stabilizes cell-cell contact for immune recognition.
- This interaction is crucial for T cell receptor-ligand engagement.
Purpose of the Study:
- To investigate the role of CD2-CD58 binding in T cell polarization and motility.
- To understand the molecular mechanisms underlying T cell scanning of antigen-presenting cells.
- To explore the redistribution of CD2 molecules during T cell activation.
Main Methods:
- Time-lapse differential interference contrast microscopy
- Immunofluorescence microscopy on living cells
- Analysis of T cell polarization and motility
- Investigation of molecular redistribution using microscopy
Main Results:
- CD2-CD58 binding induces T cell polarization and scanning motility along antigen-presenting cells.
- Scanning is dependent on T cell beta-integrin and myosin light chain kinase.
- CD2 molecules redistribute to the uropod, increasing density 100-fold upon interaction with a cellular substratum.
- No redistribution was observed for CD11a/CD18 or CD45.
Conclusions:
- CD2-CD58 interactions facilitate T cell scanning and polarization, independent of cognate antigen.
- Molecular compartmentalization of CD2 within the uropod forms a 'presynapse', prearranging the cellular activation machinery.
- This presynapse formation enhances antigen-dependent recognition and immune surveillance capabilities of T cells.