Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) inhibits TCR signaling and actin cytoskeleton reorganization.
Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) is a receptor, specific for MHC class I molecules, that inhibits lymphoid and myeloid cells. Here, we analyzed the molecular and cellular mechanisms by which ILT2 modulates T cell activation in primary CTLs and transfected T cell lines. We found that cross-linking with the TCR and the activity of Src tyrosine kinase p56(lck) were required for phosphorylation of ILT2 and subsequent recruitment of Src homology protein 1. In contrast, ILT2 triggering resulted in reduced phosphorylation of TCRzeta and linker for activation of T cells, which led to reduced TCRzeta-ZAP70 complex formation, as well as extracellular signal-related kinase 1 and 2 activation. Furthermore, ILT2 inhibited both superantigen and anti-TCR Ab-induced rearrangement of the actin cytoskeleton. The inhibitory effect mediated by ILT2 is probably concentrated at the APC-T cell interface because both TCR and ILT2 were strongly polarized toward the APC upon engagement by their specific ligands. Thus, ILT2 inhibits both signaling and cellular events involved in the activation of T cells.
Dietrich
J
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
Cella
M
M
Colonna
M
M
D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002461:Cell Line, Transformed; D016764:Cell Polarity / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D018909:src Homology Domains / Q000276:immunology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C110810:LAT protein, human; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C054979:antigen T cell receptor, zeta chain; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases