title: Transferrin' activation: bonding with transferrin receptors tunes KLRG1 function.
abstract: The inhibitory C-type lectin-like immunoreceptor KLRG1 enables mature NK cells and differentiated T cells to sense cadherin-expressing cells by ligating "classical" cadherins. Upon engagement of the KLRG1 ectodomain, an inhibitory signal emanates from the cytoplasmic immunoreceptor-tyrosine-based inhibition motif (ITIM), dampening functional responses of these lymphocytes. Malignancy-associated loss of cadherins has been proposed to relieve KLRG1-mediated inhibition of cytotoxic lymphocytes and thereby to contribute to tumor surveillance by an alternate mode of "missing self-recognition". In this issue of the European Journal of Immunology, Schweier et al. [Eur. J. Immunol. 2014. 44: 1851-1856] propose another intriguing mechanism that may relieve KLRG1-mediated inhibition in the course of lymphocyte activation. Subsequent to identification of the transferrin receptor (TfR) as a component of a high molecular mass KLRG1 complex, they demonstrate that a fraction of mouse KLRG1 molecules undergoes disulfide-bonding with TfRs and colocalises with the latter at the cell surface. In functional terms, high levels of TfRs such as those found on activated lymphocytes were found to be associated with decreased KLRG1 inhibitory function, indicating that TfRs may sequester KLRG1 from interacting with cadherins. Hence, this unexpected liaison between KLRG1 and TfR may represent a regulatory link between metabolic activation and responses of lymphocytes.
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinle
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015820:Cadherins / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000276:immunology*; D011990:Receptors, Transferrin / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*; D014168:Transferrin / Q000276:immunology*
chemical_list: D015820:Cadherins; C113413:KLRG1 protein, human; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D015534:Trans-Activators; D014168:Transferrin
keywords: KLRG1; Lymphocyte activation; NK cells; Transferrin receptor