title: Single-cell force spectroscopy: mechanical insights into the functional impacts of interactions between antigen-presenting cells and T cells.
abstract: Antigen recognition and discrimination by T lymphocyte are essential in initiating appropriate immune responses. The mechanisms underlying exquisite sensitivity and specificity of antigen discrimination are not fully elucidated but involved physical intercellular interactions between T cell and antigen-presenting cell (APC). The specificity of T-cell activation is tightly regulated by T-cell receptor (TCR) recognition of antigenic peptides in complex with major histocompatibility complex (pMHC) glycoproteins on the cell surface of APC. Antigen recognition via TCR/pMHC interactions, together with other co-receptors and co-stimulatory molecules, are spatially organized into the two-dimensional contact zone between T cells and APC, resulting in the formation of an immune synapse (IS). Here, we will review current implementations and applications of a cutting-edge biophysical technique, namely single-cell force spectroscopy (SCFS) that allows us to quantify mechanical forces of IS at APC/T cell-cell contact. The functional impacts of the mechanical strength in regulating T-cell functional activity will be discussed. We will also describe limitations of SCFS techniques, and outline recent investigations focusing on the functional roles of IS as mechanotransducer in regulating T-cell activities.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #04 Immunos, Biopolis, Singapore. lim_tong_seng@immunol.a-star.edu.sg
authors.forename: Tong Seng
authors.initials: TS
authors.lastname: Lim
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology*; D008213:Lymphocyte Activation; D040542:Mechanotransduction, Cellular / Q000276:immunology; D018625:Microscopy, Atomic Force / Q000379:methods* / Q000639:trends; D059010:Single-Cell Analysis / Q000379:methods*; D013057:Spectrum Analysis / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*