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- Title
Different inhibitory capacities of human and mouse KLRG1 are linked to distinct disulfide-mediated oligomerizations.
- Authors
Hofmann, Maike; Schweier, Oliver; Pircher, Hanspeter
- Abstract
The killer cell lectin-like receptor G1 ( KLRG1) is a cadherin-binding inhibitory receptor expressed by NK and T cells in humans and mice. Although structural and ligand-binding properties of human (h) and mouse (m) KLRG1 are very similar, KLRG1-mediated inhibition under physiological conditions is only observed with human lymphocytes. Using a well-defined in vitro system, we demonstrate here that m KLRG1 exhibits a significantly lower inhibitory capacity compared with the human homolog. Biochemical analyses further showed that m KLRG1 formed monomers and disulfide-linked dimers, trimers, and tetramers whereas h KLRG1 was exclusively present as disulfide-linked dimer. Mutational analysis revealed a crucial role of Cys62 present in the stalk region of m KLRG1 but not of h KLRG1 for oligomer formation. Strikingly, mimicking h KLRG1 by replacement of Cys62 in m KLRG1 by glutamine prevented tri- and tetramer formation and increased the inhibitory capacity. Furthermore, mutated m KLRG1 molecules that were unable to form disulfide-linked dimers at all or at a decreased level lacked inhibitory activity. These data indicate that only dimeric KLRG1 entities exhibit potent inhibitory capacities. The lower inhibitory capacity of m KLRG1 compared with h KLRG1 can thus be rationalized by a decreased proportion of dimeric entities, which can be pinpointed to a single amino acid.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 9, p2484
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201142357