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Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17852-7. doi: 10.1073/pnas.0905384106. Epub 2009 Oct 12.

Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy.

Author information

  • 1Department of New Materials and Biosystems, Max-Planck-Institute for Metals Research, Stuttgart, Germany.

Erratum in

  • Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2373.

Abstract

During adaptive immune responses, T lymphocytes recognize antigenic peptides presented by MHC molecules on antigen-presenting cells (APCs). This recognition results in the formation of a so-called immune synapse (IS) at the T-cell/APC interface, which is crucial for T-cell activation. The molecular composition of the IS has been extensively studied, but little is known about the biophysics and interaction forces between T cells and APCs. Here, we report the measurement of interaction forces between T cells and APCs employing atomic force microscopy (AFM). For these investigations, specific T cells were selected that recognize an antigenic peptide presented by MHC-class II molecules on APCs. Dynamic analysis of T-cell/APC interaction by AFM revealed that in the presence of antigen interaction forces increased from 1 to 2 nN at early time-points to a maximum of approximately 14 nN after 30 min and decreased again after 60 min. These data correlate with the kinetics of synapse formation that also reached a maximum after 30 min, as determined by high-throughput multispectral imaging flow cytometry. Because the integrin lymphocyte function antigen-1 (LFA-1) and its counterpart intercellular adhesion molecule-1 (ICAM-1) are prominent members of a mature IS, the effect of a small molecular inhibitor for LFA-1, BIRT377, was investigated. BIRT377 almost completely abolish the interaction forces, emphasizing the importance of LFA-1/ICAM-1-interactions for firm T-cell/APC adhesion. In conclusion, using biophysical measurements, this study provides precise values for the interaction forces between T cells and APCs and demonstrates that these forces develop over time and are highest when synapse formation is maximal.

PMID:
19822763
[PubMed - indexed for MEDLINE]
PMCID:
PMC2764924
Free PMC Article

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