A New Look at T Cells

Recent technological advances have shed unexpected light on the CD8⁺ T cell responses to pathogens and have raised concerns that a familiar quantitative assay is wrong. The most exciting of the new advances is the MHC tetramer. Ever since T cells were first identified, there have been attempts to show that they can be individually identified by the specificity of their antigen binding properties. The early quest failed because the ligand was not known to be an MHC–peptide complex. When the T cell receptor was eventually identified, it was ironic that it had still not been shown to bind anything. However, studies with purified receptors and complexes of antigenic peptide and MHC showed that they did bind specifically, but with low affinity and fast off-rates (1). It is now argued that during T cell recognition, the low affinity and fast off-rate are necessary to enable serial...