title: The CD85/LIR-1/ILT2 inhibitory receptor is expressed by all human T lymphocytes and down-regulates their functions.
abstract: The inhibitory molecule CD85/LIR-1/ILT2 has been detected previously on the surface of a small proportion of T lymphocytes. In this study, evidence is provided that, although only a fraction of CD3+ cells are stained by mAb specific for CD85/LIR-1/ILT2 on their surface, this inhibitory receptor is present in the cytoplasm of all T lymphocytes, and that it is detectable on the surface of all T cell clones by the M402 mAb. Biochemical analyses further demonstrate that CD85/LIR-1/ILT2 is present in all T clones analyzed, and that the protein is tyrosine-phosphorylated. Expression of mRNA coding for CD85/LIR-1/ILT2 has been assessed by RT-PCR. Notably, in the NKL cell line and in one T cell clone, amplification of the messenger required 30 cycles only, whereas, in other T cell clones, an amplification product was detected by increasing the number of cycles. CD85/LIR-1/ILT2 inhibits CD3/TCR-mediated activation in both CD4+ and CD8+ clones, and it down-regulates Ag recognition by CD8+ cells in a clonally distributed fashion. Addition of anti-ILT2 HP-F1 mAb in the cytolytic assay enhances target cell lysis mediated by Ag-specific CTL. This could be due to interference of the mAb with receptor/ligand interactions. In contrast, HP-F1 mAb cross-linking triggers inhibitory signals that reduce cytotoxicity. CD85/LIR-1/ILT2 also controls responses to recall Ags and, in low responders, its engagement sharply increases T cell proliferation. The inhibitory function of the molecule is also confirmed by its ability to reduce CD3/TCR-induced intracellular Ca2+ mobilization.
authors.affiliation: Department of Experimental Medicine, University of Genova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Saverino
authors.forename: M
authors.initials: M
authors.lastname: Fabbi
authors.forename: F
authors.initials: F
authors.lastname: Ghiotto
authors.forename: A
authors.initials: A
authors.lastname: Merlo
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: D
authors.initials: D
authors.lastname: Zarcone
authors.forename: C
authors.initials: C
authors.lastname: Tenca
authors.forename: M
authors.initials: M
authors.lastname: Tiso
authors.forename: G
authors.initials: G
authors.lastname: Santoro
authors.forename: G
authors.initials: G
authors.lastname: Anastasi
authors.forename: D
authors.initials: D
authors.lastname: Cosman
authors.forename: C E
authors.initials: CE
authors.lastname: Grossi
authors.forename: E
authors.initials: E
authors.lastname: Ciccone
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis / Q000378:metabolism; D015703:Antigens, CD; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D020013:Calcium Signaling / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology; D007399:Interphase / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D018984:Epitopes, T-Lymphocyte; D007166:Immunosuppressive Agents; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011971:Receptors, Immunologic