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Functional consequences of the interaction between T-cell antigen receptors and Fc gamma Rs on T cells
K Kwack1, J S Verbeek, J G van de Winkel
1Department of Pathology College of Medicine, University of Iowa, Iowa City, USA.
Abstract:
Two series of experiments are presented indicating that Fc gamma II receptors can interfere with the antigen receptor-induced signaling on T cells. It has been previously described that a 13 amino acid motif on the cytoplasmic portion of Fc gamma II beta 1 can abrogate the antigen receptor-initiated signals mediated through consensus motifs present on the cytoplasmic portion of Ig alpha and Ig beta chains. Similar activating motifs are crucial to T-cell receptor (TCR) signaling. A splenic gamma/delta T-cell hybridoma that expressed the Fc gamma RII beta 1 receptor helped to establish that this receptor can also interfere with TCR-induced activation. The cytoplasmic portion of human Fc gamma RIIa has an activation motif similar to the activation motifs present on the TCR. Using a transgenic mouse in which the T cells express the human Fc gamma RIIa transgene, we demonstrated that despite the common activation motif, the TCR and human Fc gamma RIIa-induced signals are different. Additionally, the human Fc gamma RIIa expressing T cells exhibit an enhanced TCR response both in vitro and in vivo.
Insights
Fc gamma II receptors can interfere with T-cell signaling. Experiments show these receptors can modulate T-cell receptor activation, impacting immune responses.
Area of Science:
- Immunology
- Cell Signaling
Background:
- Fc gamma II receptors are known to interact with immune cells.
- The cytoplasmic domains of Fc gamma II beta 1 and T-cell receptors (TCRs) contain motifs crucial for signaling.
- Previous studies indicated Fc gamma II beta 1 can inhibit antigen receptor signaling.
Purpose of the Study:
- To investigate the interference of Fc gamma II receptors with T-cell receptor (TCR)-induced signaling.
- To determine if Fc gamma II receptors can modulate TCR signaling pathways.
- To analyze the signaling differences between TCR and Fc gamma RIIa activation.
Main Methods:
- Utilizing a splenic gamma/delta T-cell hybridoma expressing Fc gamma RII beta 1.
- Employing transgenic mice with T cells expressing human Fc gamma RIIa.
- Conducting in vitro and in vivo experiments to assess T-cell responses.
Main Results:
- Fc gamma II beta 1 receptor expression interfered with TCR-induced activation in a T-cell hybridoma.
- Human Fc gamma RIIa and TCR signaling pathways, despite sharing activation motifs, were found to be distinct.
- T cells expressing human Fc gamma RIIa showed an augmented TCR response both in vitro and in vivo.
Conclusions:
- Fc gamma II receptors play a role in modulating T-cell signaling.
- The interaction between Fc gamma II receptors and TCR signaling is complex and context-dependent.
- Human Fc gamma RIIa expression can enhance T-cell responses, suggesting potential therapeutic implications.