J. Exp. Med., Volume 186, Number 11, December 1, 1997 1809-1818

A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells

By Marco Colonna,^* Francisco Navarro, Teresa Bellón, Manuel Llano, Pilar García, Jacqueline Samaridis,^* Lena Angman,^* Marina Cella,^* and Miguel López-Botet

From the ^* Basel Institute for Immunology, Basel CH-4005, Switzerland; and  Hospital Universitario de la Princesa, 28006 Madrid, Spain

Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca²⁺ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

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• Chwae, Y.-J., Chang, M. J., Park, S. M., Yoon, H., Park, H.-J., Kim, S. J., Kim, J. (2002). Molecular Mechanism of the Activation-Induced Cell Death Inhibition Mediated by a p70 Inhibitory Killer Cell Ig-Like Receptor in Jurkat T Cells. J. Immunol. 169: 3726-3735 [Abstract] [Full Text]  
• Guerra, N., Michel, F., Gati, A., Gaudin, C., Mishal, Z., Escudier, B., Acuto, O., Chouaib, S., Caignard, A. (2002). Engagement of the inhibitory receptor CD158a interrupts TCR signaling, preventing dynamic membrane reorganization in CTL/tumor cell interaction. Blood 100: 2874-2881 [Abstract] [Full Text]  
• Farag, S. S., Fehniger, T. A., Ruggeri, L., Velardi, A., Caligiuri, M. A. (2002). Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 100: 1935-1947 [Abstract] [Full Text]  
• Nikolova, M., Musette, P., Bagot, M., Boumsell, L., Bensussan, A. (2002). Engagement of ILT2/CD85j in Sezary syndrome cells inhibits their CD3/TCR signaling. Blood 100: 1019-1025 [Abstract] [Full Text]  
• Dulphy, N., Rabian, C., Douay, C., Flinois, O., Laoussadi, S., Kuipers, J., Tamouza, R., Charron, D., Toubert, A. (2002). Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis. Int Immunol 14: 471-479 [Abstract] [Full Text]  
• Miller, I., Hatzivassiliou, G., Cattoretti, G., Mendelsohn, C., Dalla-Favera, R. (2002). IRTAs: a new family of immunoglobulinlike receptors differentially expressed in B cells. Blood 99: 2662-2669 [Abstract] [Full Text]  
• Bellon, T., Kitzig, F., Sayos, J., Lopez-Botet, M. (2002). Mutational Analysis of Immunoreceptor Tyrosine-Based Inhibition Motifs of the Ig-Like Transcript 2 (CD85j) Leukocyte Receptor. J. Immunol. 168: 3351-3359 [Abstract] [Full Text]  
• Markel, G., Lieberman, N., Katz, G., Arnon, T. I., Lotem, M., Drize, O., Blumberg, R. S., Bar-Haim, E., Mader, R., Eisenbach, L., Mandelboim, O. (2002). CD66a Interactions Between Human Melanoma and NK Cells: A Novel Class I MHC-Independent Inhibitory Mechanism of Cytotoxicity. J. Immunol. 168: 2803-2810 [Abstract] [Full Text]  
• Rieger, L., Hofmeister, V., Probe, C., Dietl, J., Weiss, E.H., Steck, T., Kammerer, U. (2002). Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E. Mol Hum Reprod 8: 255-261 [Abstract] [Full Text]  
• Tedla, N., Gibson, K., McNeil, H. P., Cosman, D., Borges, L., Arm, J. P. (2002). The Co-Expression of Activating and Inhibitory Leukocyte Immunoglobulin-Like Receptors in Rheumatoid Synovium. Am. J. Pathol. 160: 425-431 [Abstract] [Full Text]  
• Urosevic, M., Willers, J., Mueller, B., Kempf, W., Burg, G., Dummer, R. (2002). HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas. Blood 99: 609-617 [Abstract] [Full Text]  
• Kim, N., Takami, M., Rho, J., Josien, R., Choi, Y. (2002). A Novel Member of the Leukocyte Receptor Complex Regulates Osteoclast Differentiation. JEM 195: 201-209 [Abstract] [Full Text]  
• Saverino, D., Merlo, A., Bruno, S., Pistoia, V., Grossi, C. E., Ciccone, E. (2002). Dual Effect of CD85/Leukocyte Ig-Like Receptor-1/Ig-Like Transcript 2 and CD152 (CTLA-4) on Cytokine Production by Antigen-Stimulated Human T Cells. J. Immunol. 168: 207-215 [Abstract] [Full Text]  
• Hurks, H. M. H., Valter, M. M., Wilson, L., Hilgert, I., van den Elsen, P. J., Jager, M. J. (2001). Uveal Melanoma: No Expression of HLA-G. IOVS 42: 3081-3084 [Abstract] [Full Text]  
• Allen, R. L., Raine, T., Haude, A., Trowsdale, J., Wilson, M. J. (2001). Cutting Edge: Leukocyte Receptor Complex-Encoded Immunomodulatory Receptors Show Differing Specificity for Alternative HLA-B27 Structures. J. Immunol. 167: 5543-5547 [Abstract] [Full Text]  
• Canavez, F., Young, N. T., Guethlein, L. A., Rajalingam, R., Khakoo, S. I., Shum, B. P., Parham, P. (2001). Comparison of Chimpanzee and Human Leukocyte Ig-Like Receptor Genes Reveals Framework and Rapidly Evolving Genes. J. Immunol. 167: 5786-5794 [Abstract] [Full Text]  
• Devergne, O., Coulomb-L'Hermine, A., Capel, F., Moussa, M., Capron, F. (2001). Expression of Epstein-Barr Virus-Induced Gene 3, an Interleukin-12 p40-Related Molecule, throughout Human Pregnancy : Involvement of Syncytiotrophoblasts and Extravillous Trophoblasts. Am. J. Pathol. 159: 1763-1776 [Abstract] [Full Text]  
• Vyas, Y. M., Mehta, K. M., Morgan, M., Maniar, H., Butros, L., Jung, S., Burkhardt, J. K., Dupont, B. (2001). Spatial Organization of Signal Transduction Molecules in the NK Cell Immune Synapses During MHC Class I-Regulated Noncytolytic and Cytolytic Interactions. J. Immunol. 167: 4358-4367 [Abstract] [Full Text]  
• Merlo, A., Saverino, D., Tenca, C., Grossi, C. E., Bruno, S., Ciccone, E. (2001). CD85/LIR-1/ILT2 and CD152 (Cytotoxic T Lymphocyte Antigen 4) Inhibitory Molecules Down-Regulate the Cytolytic Activity of Human CD4+ T-Cell Clones Specific for Mycobacterium tuberculosis. Infect. Immun. 69: 6022-6029 [Abstract] [Full Text]  

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