Major histocompatibility complex class I molecules modulate activation threshold and early signaling of T cell antigen receptor-γ/δ stimulated by nonpeptidic ligands

Ilaria Carena, Abdijapar Shamshiev, Alena Donda, Marco Colonna, Gennaro De Libero

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1769-1774
Number of pages6
JournalJournal of Experimental Medicine
Volume186
Issue number10
DOIs
StatePublished - Nov 17 1997

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