Interaction of KLRG1 with E-cadherin: New functional and structural insights

Stephan Rosshart, Maike Hofmann, Oliver Schweier, Anne Kathrin Pfaff, Keiko Yoshimoto, Tsutomu Takeuchi, Eszter Molnar, Wolfgang W. Schamel, Hanspeter Pircher

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3354-3364
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number12
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • E-cadherin
  • Killer cell lectin-like receptor
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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