Interaction of KLRG1 with E-cadherin: new functional and structural insights.
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 Y(7)F-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.
Rosshart
Stephan
S
Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Germany.
Hofmann
Maike
M
Schweier
Oliver
O
Pfaff
Anne-Kathrin
AK
Yoshimoto
Keiko
K
Takeuchi
Tsutomu
T
Molnar
Eszter
E
Schamel
Wolfgang W
WW
Pircher
Hanspeter
H
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017353:Gene Deletion; D017930:Genes, Reporter / Q000235:genetics; D037181:Lectins, C-Type; D051379:Mice; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D017252:CD3 Complex; D015820:Cadherins; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic