Major histocompatibility complex class I molecules modulate activation threshold and early signaling of T cell antigen receptor-gamma/delta stimulated by nonpeptidic ligands.
Killer cell inhibitory receptors and CD94-NKG2-A/B heterodimers are major histocompatibility complex class I-specific inhibitory receptors expressed by natural killer cells, T cell antigen receptor (TCR)-gamma/delta cells, and a subset of TCR-alpha/beta cells. We studied the functional interaction between TCR-gamma/delta and CD94, this inhibitory receptor being expressed on the majority of gamma/delta T cells. When engaged by human histocompatibility leukocyte antigen class I molecules, CD94 downmodulates activation of human TCR-gamma/delta by phosphorylated ligands. CD94-mediated inhibition is more effective at low than at high doses of TCR ligand, which may focus T cell responses towards antigen-presenting cells presenting high amounts of antigen. CD94 engagement has major effects on TCR signaling cascade. It facilitates recruitment of SHP-1 phosphatase to TCR-CD3 complex and affects phosphorylation of Lck and ZAP-70 kinase, but not of CD3 zeta chain upon TCR triggering. These events may cause abortion of proximal TCR-mediated signaling and set a higher TCR activation threshold.
Carena
I
I
Experimental Immunology, Department of Research, University Hospital, Basel, Switzerland.
Shamshiev
A
A
Donda
A
A
Colonna
M
M
Libero
G D
GD
D015703:Antigens, CD / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D006680:HLA Antigens / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides / Q000276:immunology / 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; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D054340:Receptors, KIR; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; 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