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Published on: April 25, 2018
Cytotoxic T lymphocytes form an antigen-independent ring junction
Kristina Somersalo1, Nadja Anikeeva, Tasha N Sims
1Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA.
Insights
Cytotoxic T lymphocytes form ring junctions at cell-cell interfaces, crucial for antigen hunting. This interaction, involving ICAM-1 and MICA, differs between CD8(+) and CD4(+) T cells, impacting T cell reactivity.
Area of Science:
- Immunology
- Cell Biology
- T cell activation
Background:
- Immunological synapses are critical for T cell-mediated immunity.
- CD8(+) cytotoxic T lymphocytes (CTLs) use synapses for targeted killing.
- Understanding synapse formation in CTLs is key to immune response.
Purpose of the Study:
- To investigate the formation of ring junctions in human CTLs and helper T cells.
- To compare CTL and helper T cell interactions with artificial substrates presenting ICAM-1.
- To explore the role of ICAM-1 and MICA in immunological synapse formation.
Main Methods:
- Utilized supported planar bilayers with ICAM-1 to mimic cell-cell interactions.
- Compared the synapse formation of CD8(+) CTLs and CD4(+) helper T cells.
- Analyzed the composition and function of the formed ring junctions.
Main Results:
- CTLs formed ring junctions, resembling peripheral supramolecular activation clusters (pSMACs), particularly at high ICAM-1 densities.
- MICA facilitated ring junction formation at lower ICAM-1 densities.
- Activated CD8(+) T cells formed five times more ring junctions than activated CD4(+) T cells.
- These ring junctions contained LFA-1 and talin but did not induce granule polarization.
Conclusions:
- CTLs form distinct ring junctions that differ from canonical immunological synapses.
- The observed ring junction formation has implications for CTLs' ability to hunt for antigen in tissues.
- Dysregulation of this process may affect CTL reactivity and immune surveillance.
Abstract:
Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8(+) cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic agents to the synaptic cleft. We have investigated the interaction of human CTLs and helper T cells with supported planar bilayers containing ICAM-1. This artificial substrate provides identical ligands to CD4(+) and CD8(+) T cells, allowing a quantitative comparison. We found that cytotoxic T lymphocytes form a ring junction similar to a pSMAC in response to high surface densities of ICAM-1 in the planar bilayer. MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are upregulated in tissues by inflammation- and stress-associated signaling, respectively. Activated CD8(+) T cells formed fivefold more ring junctions than did activated CD4(+) T cells. The ring junction contained lymphocyte function associated antigen-1 and talin, but did not trigger polarization and granule translocation to the interface. This result has specific implications for the mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this process may alter CTL reactivity.
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