Single-cell force spectroscopy: mechanical insights into the functional impacts of interactions between antigen-presenting cells and T cells

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.