TY - JOUR
T1 - Major histocompatibility complex class I molecules modulate activation threshold and early signaling of T cell antigen receptor-γ/δ stimulated by nonpeptidic ligands
AU - Carena, Ilaria
AU - Shamshiev, Abdijapar
AU - Donda, Alena
AU - Colonna, Marco
AU - De Libero, Gennaro
PY - 1997/11/17
Y1 - 1997/11/17
N2 - 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)-γ/δ cells, and a subset of TCR-α/β cells. We studied the functional interaction between TCR-γ/δ and CD94, this inhibitory receptor being expressed on the majority of γ/δ T cells. When engaged by human histocompatibility leukocyte antigen class I molecules, CD94 downmodulates activation of human TCR-γ/δ 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 ζ chain upon TCR triggering. These events may cause abortion of proximal TCR-mediated signaling and set a higher TCR activation threshold.
AB - 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)-γ/δ cells, and a subset of TCR-α/β cells. We studied the functional interaction between TCR-γ/δ and CD94, this inhibitory receptor being expressed on the majority of γ/δ T cells. When engaged by human histocompatibility leukocyte antigen class I molecules, CD94 downmodulates activation of human TCR-γ/δ 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 ζ chain upon TCR triggering. These events may cause abortion of proximal TCR-mediated signaling and set a higher TCR activation threshold.
UR - http://www.scopus.com/inward/record.url?scp=0030695945&partnerID=8YFLogxK
U2 - 10.1084/jem.186.10.1769
DO - 10.1084/jem.186.10.1769
M3 - Article
C2 - 9362537
AN - SCOPUS:0030695945
SN - 0022-1007
VL - 186
SP - 1769
EP - 1774
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -