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 (TCRs) with complexes of peptide and major histocompatibility complex (MHC) molecules displayed on the cell surface of antigen-presenting cells (APCs) [1]. An unresolved question of antigen recognition by T cells is how TCR triggering actually occurs at the cell-cell contact area. We visualized T-cell-APC contact sites using confocal microscopy and three-dimensional reconstruction of z-sections. We show the rapid formation of a specialized signaling domain at the T-cell-APC contact site that is characterized by a broad and 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 phosphorylation area. Remarkably, the highly expressed phosphatase CD45 is excluded from the signaling domain. Our results indicate that physiological TCR triggering at the T-cell-APC contact site is the result of a localized alteration in the balance between cellular kinases and phosphatases. We therefore provide experimental evidence to support current models of T-cell activation based on CD45 exclusion from the TCR signaling area [2] [3] [4].
Leupin
O
O
BIL Research Center, Institute of Biochemistry, University of Lausanne, Epalinges, 1066, Switzerland.
Zaru
R
R
Laroche
T
T
Müller
S
S
Valitutti
S
S
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens