The CD85/LIR-1/ILT2 Inhibitory Receptor Is Expressed by All Human T Lymphocytes and Down-Regulates Their Functions

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 p...

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Published in:The Journal of immunology (1950) 2000-10, Vol.165 (7), p.3742-3755
Main Authors: Saverino, Daniele, Fabbi, Marina, Ghiotto, Fabio, Merlo, Andrea, Bruno, Silvia, Zarcone, Daniela, Tenca, Claudya, Tiso, Micaela, Santoro, Giuseppe, Anastasi, Giuseppe, Cosman, David, Grossi, Carlo E, Ciccone, Ermanno
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - analysis
Antibodies, Monoclonal - metabolism
Antigens, CD
Calcium Signaling - immunology
CD3 antigen
CD3 Complex - physiology
CD4-Positive T-Lymphocytes - immunology
CD85 antigen
Clone Cells - immunology
Clone Cells - metabolism
Cytoplasm - immunology
Cytoplasm - metabolism
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic - immunology
Down-Regulation - immunology
Epitopes, T-Lymphocyte - immunology
Humans
ILT2 protein
Immunologic Memory - immunology
Immunosuppressive Agents - immunology
Interphase - immunology
Intracellular Fluid - immunology
Intracellular Fluid - metabolism
Leukocyte Immunoglobulin-like Receptor B1
LIR1 protein
Lymphocyte Activation - immunology
Membrane Glycoproteins - immunology
Membrane Glycoproteins - metabolism
Receptor-CD3 Complex, Antigen, T-Cell - physiology
Receptors, Immunologic - biosynthesis
Receptors, Immunologic - genetics
Receptors, Immunologic - immunology
Receptors, Immunologic - metabolism
RNA, Messenger - biosynthesis
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.165.7.3742