Interaction of KLRG1 with E‐cadherin: New functional and structural insights |
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| Authors: | Stephan Rosshart Maike Hofmann Oliver Schweier Anne‐Kathrin Pfaff Keiko Yoshimoto Tsutomu Takeuchi Eszter Molnar Wolfgang W Schamel Hanspeter Pircher |
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| Institution: | 1. Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Germany;2. Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan;3. Max‐Planck‐Institute of Immunobiology and University of Freiburg, Germany |
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| Abstract: | The killer cell lectin‐like receptor G1 (KLRG1) is an inhibitory receptor expressed by memory T cells and NK cells in man and mice. It is frequently used as a cell differentiation marker and members of the cadherin family are ligands for KLRG1. The present study provides new insights into the interaction of mouse KLRG1 with E‐cadherin. Firstly, we demonstrate that co‐engagement of KLRG1 and CD3/TCR in a spatially linked manner was required for inhibition arguing against the notion that KLRG1‐ligation per se transmits inhibitory signals. Secondly, experiments with T cells carrying Y7F‐mutant KLRG1 molecules with a replacement of the tyrosine residue to phenylalanine in the single ITIM indicated that the inhibitory activity of KLRG1 is counteracted to some degree by increased interaction of KLRG1+ T cells with E‐cadherin expressing target cells. Thirdly, we demonstrate that deletion of the first or the second external domain of E‐cadherin abolished reactivity in KLRG1‐reporter cell assays. Finally, we made the intriguing observation that KLRG1 formed multimeric protein complexes in T cells in addition to the previously described mono‐ and dimeric molecules. |
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| Keywords: | E‐cadherin Killer cell lectin‐like receptor T cells |
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