title: Insights into T cell recognition of antigen: significance of two-dimensional kinetic parameters.
abstract: The T cell receptor (TCR) interacts with peptide-major histocompatibility complex (pMHC) to enable T cell development and trigger adaptive immune responses. For this reason, TCR:pMHC interactions have been intensely studied for over two decades. However, the details of how various binding parameters impact T cell activation remain elusive. Most measurements were made using recombinant proteins by surface plasmon resonance, a three-dimensional (3D) technique in which fluid-phase receptors and ligands are removed from their cellular environment. This approach found TCR:pMHC interactions with relatively low affinities and slow off-rates for agonist peptides. Newer generation techniques have analyzed TCR:pMHC interactions in two dimensions (2D), with both proteins anchored in apposing plasma membranes. These approaches reveal in situ TCR:pMHC interaction kinetics that are of high affinity and exhibit rapid on- and off-rates upon interaction with agonist ligands. Importantly, 2D binding parameters correlate better with T cell functional responses to a spectrum of ligands than 3D measures.
authors.affiliation: Department of Microbiology and Immunology, Emory University Atlanta, GA, USA.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Edwards
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Zarnitsyna
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hood
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu