T cell triggering: insights from 2D kinetics analysis of molecular interactions

Author: Veronika Zarnitsyna

Date: 8/9/2012

Journal:Physical Biology


DOI: 10.1088/1478-3975/9/4/045005.

Link: http://iopscience.iop.org/article/10.1088/1478-3975/9/4/045005/meta;jsessionid=92F52A37E24C57E2E53E1DE7D2F7BCDA.c1


Interaction of the T cell receptor (TCR) with pathogen-derived peptide presented by the major histocompatibility complex (pMHC) molecule is central to adaptive immunity as it initiates intracellular signaling to trigger T cell response to infection. Kinetic parameters of this interaction have been under intensive investigation for more than two decades using soluble pMHCs and/or TCRs with at least one of them in the solution (three-dimensional (3D) methods). Recently, several techniques have been developed to enable kinetic analysis on live T cells with pMHCs presented by surrogate antigen presenting cells (APCs) or supported planar lipid bilayers (two-dimensional (2D) methods). Comparison of 2D versus 3D parameters reveals drastic differences with broader ranges of 2D affinities and on-rates and orders of magnitude faster 2D off-rates for functionally distinct pMHCs. Here we review new 2D data and discuss how it may impact previously developed models of T cell discrimination between pMHCs of different potencies.