Setting the path – How qualitative and quantitative differences in TCR-pMHC interactions regulate T cell immune responses

The engagement of TCRs with pMHC complexes is often considered a checkpoint requirement for T cell activation, with cytokines and co-stimulation regulating the acquisition of effector functions and long-term T cell memory formation. Recent experiments are beginning to demonstrate that the quality of the TCR-pMHC interaction (i.e., the TCR-pMHC dwell time), as well as the quantity and kinetics of pMHC can have profound influences on generation of specific T cell effector subsets and T cell memory formation. In light of these new discoveries, our intention is to extensively review the current understandings of T cell activation, with an emphasis on how differences in antigen recognition impacts the T cell immune response. Collectively, these reviews will also raise awareness of the key questions of T cell recognition of antigen and T cell activation that remain unresolved.

Our motivation to initiate this Research Topics is to discuss four critical parameters that shape T cell responses following the recognition of antigen: the quality of the TCR-pMHC interaction; the concentration of antigen; the duration of antigen presentation; and the types of antigen presenting cells that display the pMHC ligands to T cells. In addition, we encourage an open discussion regarding unresolved issues of T cell priming. Each participant is encouraged to discuss any aspect of T cell activation they would like to cover. By selecting the participants with a wide range of expertise, our intention is to cover all of the major questions in the field.