The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing.

Abstract

Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the αβTCR, antigen induces a conformational change at the CD3 subunits (CD3 CC) that is absolutely required for αβTCR activation. Here, we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse G8 or the human Vγ9Vδ2 γδTCR. We find that there is a fundamental difference between the activation mechanisms of the αβTCR and γδTCR that map to the constant regions of the TCRαβ/γδ heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal anti-CD3 promoted proximal γδTCR signaling but inhibited cytokine secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor cell lysis by activated human γδ T cells. Thus, manipulation of the CD3 CC might be exploited to improve clinical γδ T cell-based immunotherapies.

• Authors: Elaine P Dopfer, Frederike A Hartl, Hans-Heinrich Oberg, Gabrielle M Siegers, O Sascha Yousefi, Sylvia Kock, Gina J Fiala, Beatriz Garcillán, Andrew Sandstrom, Balbino Alarcón, Jose R Regueiro, Dieter Kabelitz, Erin J Adams, Susana Minguet, Daniela Wesch, Paul Fisch, Wolfgang W A Schamel
• Journal: Cell reports (Cell Rep) Vol. 7 Issue 5 Pg. 1704-1715 (Jun 12 2014) ISSN: 2211-1247 [Electronic] United States
• PMID: 24857663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• CD3 Complex
• Receptor-CD3 Complex, Antigen, T-Cell
• Receptors, Antigen, T-Cell, gamma-delta

Topics

• Animals
• CD3 Complex (chemistry, immunology)
• Cell Line
• Cytotoxicity, Immunologic
• Humans
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• Protein Binding
• Protein Conformation
• Receptor-CD3 Complex, Antigen, T-Cell (chemistry, immunology)
• Receptors, Antigen, T-Cell, gamma-delta (chemistry, immunology)
• T-Lymphocytes (immunology)