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Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases
- Source :
- European Journal of Immunology, European Journal of Immunology, Wiley-VCH Verlag, 1998, 28 (1), pp.264-76. ⟨10.1002/(SICI)1521-4141(199801)28:013.0.CO;2-O⟩, European Journal of Immunology, 1998, 28 (1), pp.264-76. ⟨10.1002/(SICI)1521-4141(199801)28:013.0.CO;2-O⟩
- Publication Year :
- 1998
-
Abstract
- International audience; Subsets of T and natural killer (NK) lymphocytes express the CD94-NKG2A heterodimer, a receptor for major histocompatibility complex class I molecules. We show here that engagement of the CD94-NKG2A heterodimer inhibits both antigen-driven tumor necrosis factor (TNF) release and cytotoxicity on melanoma-specific human T cell clones. Similarly, CD16-mediated NK cell cytotoxicity is extinguished by cross-linking of the CD94-NKG2A heterodimer. Combining in vivo and in vitro analysis, we report that both I/VxYxxL immunoreceptor tyrosine-based inhibition motifs (ITIM) present in the NKG2A intracytoplasmic domain associate upon tyrosine phosphorylation with the protein tyrosine phosphatases SHP-1 and SHP-2, but not with the polyinositol phosphatase SHIP Determination of the dissociation constant, using surface plasmon resonance analysis, indicates that NKG2A phospho-ITIM interact directly with the SH2 domains of SHP-1 and SHP-2 with a high affinity. Engagement of the CD94-NKG2A heterodimer therefore appears as a protein-tyrosine phosphatase-based strategy that negatively regulates both antigen-induced T cell response and antibody-induced NK cell cytotoxicity. Our results suggest that this inhibitory pathway sets the threshold of T and NK cell activation.
- Subjects :
- [SDV]Life Sciences [q-bio]
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein tyrosine phosphatase
Lymphocyte Activation
Tumor-infiltrating lymphocytes
chemistry.chemical_compound
Interleukin 21
Immunoreceptor tyrosine-based activation motif
Tumor Cells, Cultured
Immunology and Allergy
Melanoma
Membrane Glycoproteins
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Intracellular Signaling Peptides and Proteins
Cell biology
[SDV] Life Sciences [q-bio]
Killer Cells, Natural
medicine.anatomical_structure
CD94/NKG2
Immunoreceptor tyrosine-based inhibitory motif
Dimerization
NK Cell Lectin-Like Receptor Subfamily D
Immunosuppressive Agents
Protein Binding
Macromolecular Substances
T cell
Recombinant Fusion Proteins
Immunology
Molecular Sequence Data
Biology
Lymphocytes, Tumor-Infiltrating
Antigens, CD
Killercell inhibitory receptor TIL
medicine
Animals
Humans
Lectins, C-Type
Amino Acid Sequence
Lymphokine-activated killer cell
Tumor Necrosis Factor-alpha
Receptors, IgG
Antibody-Dependent Cell Cytotoxicity
Tyrosine phosphorylation
Immunoreceptor tyrosine-based inhibition motif KIR
Rats
Kinetics
chemistry
Immunoreceptor tyrosine-based inhibition motif / Phosphatase / Tumor immunology / Melanoma antigen / Killer cell inhibitory receptor Immunoreceptor tyrosine-based activation motif ITIM
Protein Tyrosine Phosphatases
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 00142980 and 15214141
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.doi.dedup.....0ec524ac11da2258c0dd31863eeefe95