Exclusion of CD45 from the T-cell receptor signaling area in antigen-stimulated T lymphocytes

T lymphocytes are activated by the engagement of their antigen receptors (T CRs) with complexes of peptide and major histocompatibility complex (MHC) m olecules displayed on the cell surface of antigen-presenting cells (APCs) [ 1]. An unresolved question of antigen recognition by T cells is how TCR tri ggering actually occurs at the cell-cell contact area. We visualized T-cell -APC contact sites using confocal microscopy and three-dimensional reconstr uction of z-sections. We show the rapid formation of a specialized signalin g domain at the T-cell-APC contact site that is characterized by a broad an d sustained area of tyrosine phosphorylation. The T-lymphocyte cell-surface molecule CD2 is rapidly recruited into this signaling domain, whereas TCRs progressively percolate from the entire T-cell surface into the phosphoryl ation area. Remarkably, the highly expressed phosphatase CD45 is excluded f rom the signaling domain. Our results indicate that physiological TCR trigg ering at the T-cell-APC contact site is the result of a localized alteratio n in the balance between cellular kinases and phosphatases. We therefore pr ovide experimental evidence to support current models of T-cell activation based on CD45 exclusion from the TCR signaling area [2-4].