A natural killer cell receptor specific for a major histocompatibility complex class I molecule.

Target cell expression of major histocompatibility complex (MHC) class I molecules correlates with resistance to lysis by natural killer (NK) cells. Prior functional studies of the murine NK cell surface molecule, Ly-49, suggested its role in downregulating NK cell cytotoxicity by specifically interacting with target cell H-2Dd molecules. In support of this hypothesis, we now demonstrate a physical interaction between H-2Dd and Ly-49 in both qualitative and quantitative cell-cell binding assays employing a stable transfected Chinese hamster ovary (CHO) cell line expressing Ly-49 and MHC class I transfected target cells. Binding occurred only when CHO cells expressed Ly-49 at high levels and targets expressed H-2Dd by transfection. Monoclonal antibody blocking experiments confirmed this interaction. These studies indicate that the specificity of natural killing is influenced by NK cell receptors that engage target cell MHC class I molecules

Aut-invariant quasimorphisms on free products

Acknowledgements I like to thank Jarek Ke ̨dra and Benjamin Martin for their continued support and all their helpful com- ments. This work was partly funded by the Leverhulme Trust Research Project Grant RPG-2017-159.Peer reviewedPublisher PD

Qualitative counting closed geodesics

Open Access via the Springer Compact Agreement Acknowledgements This work was partly funded by the Leverhulme Trust Research Project Grant RPG-2017-159. MM is supported by the grant Sonatina 2018/28/C/ST1/00542 funded by Narodowe Centrum Nauki. MM and JK were partially supported by SFB 1085 “Higher Invariants” funded by Deutsche Forschungsgemeinschaft.Peer reviewedPublisher PD

Filling the gap? Korporatismus und neue Akteure in der Politikgestaltung

'In diesem Beitrag geht es darum zu prüfen, inwieweit sich mit der aus dem (Teil-)Rückzug der korporatistischen Akteure vom Politikgestaltungsprozess entstehenden Lücke Möglichkeiten der Einflussnahme für andere Akteure (Think Tanks, Politikberater, Lobbyisten) ergeben. Grundüberlegung ist, dass die für Österreich lange Zeit prägende Rolle der Sozialpartnerschaft empirisch nachvollziehbar an Boden verloren hat, was aber nicht selbstverständlich zugunsten alternativer Gestaltungsmuster geschieht, zumal die 'neuen' Anbieter oft einer Nachfrage entsprechen, die - Stichwort Europäisierung - erst in jüngerer Zeit stark zugenommen hat. In ihren 'natürlichen' Kernbereichen Wirtschaftspolitik und Sozialpolitik, so die These, sind die korporatistischen Akteure als Agenda-Setter und Politikberater nach wie vor dominant vertreten.' (Autorenreferat)'For some time past, the role of social partnership as a player in policy making has significantly declined. It would be false, however, to conclude from the gradual loss in importance of a general demise of Austria's version of corporatism. The (partial) retreat of social partnership from several policy fields does not necessarily take place at the benefit of alternative providers, such as think tanks, policy advisors, and lobbyists. It is argued that, with the background of Europeanisation, the 'new' actors supply the growing demand of expertise and advice in various fields, frequently complementing established players rather than replacing them. The 'old', corporatist actors are now as before undisputed advisors in their genuine core businesses economic and social policy.' (author's abstract)

Ly49A Transgenic Mice Provide Evidence for a Major Histocompatibility Complex–dependent Education Process in Natural Killer Cell Development

The Ly49 natural killer (NK) cell receptors are class I MHC–specific inhibitory receptors that are distributed to overlapping NK cell subsets. The formation of the Ly49 receptor repertoire was examined with transgenic mice that express Ly49A in all NK cells. In MHC class I–deficient mice, the Ly49A transgene did not prevent expression of endogenous Ly49 genes. However, in H-2d mice that express a Ly49A ligand, the transgene caused clear alterations in the endogenous Ly49 repertoire. The frequency of NK cells expressing another H-2d–specific receptor, Ly49G2+, was substantially reduced. Reduced numbers of cells expressing endogenous Ly49A was suggested by reduced endogenous Ly49A mRNA levels. These results support the existence of an MHC-dependent education process that limits the number of NK cells that coexpress multiple self-specific Ly49 receptors. Ligand-dependent downregulation of Ly49 cell surface levels was also examined. Cell-surface downregulation occurred even when the transgene was expressed at low levels. The results demonstrate that downregulation of Ly49A cell surface levels is a posttranscriptional event, and argue against a model in which Ly49 receptors are calibrated to specific cell surface levels depending on the available class I ligands

Expression of Natural Killer Receptor Alleles at Different Ly49 Loci Occurs Independently and Is Regulated by Major Histocompatibility Complex Class I Molecules

Ly49 receptor genes are expressed by subsets of natural killer (NK) cells in an overlapping fashion, accounting for the capacity of NK subsets to attack host cells that have selectively downregulated self–major histocompatibility complex (MHC) class I molecules. It was shown previously that most NK cells express only one or the other allele of a given Ly49 gene, while a smaller population expresses both alleles. However, the methods used to detect monoallelic and biallelic cells were nonquantitative. Here, new allele-specific antibodies were used to provide the first quantitative examination of biallelic and monoallelic expression of Ly49A and Ly49G2. The results demonstrate conclusively that most Ly49A+ and Ly49G2+ NK cells express the corresponding gene in a monoallelic fashion, with a smaller subset expressing both alleles. Unexpectedly, biallelic Ly49A+ NK cells were more numerous than predicted by completely independent allelic expression, suggesting some heterogeneity among NK progenitors in the potential to express a given Ly49 gene. The data also show that cells expressing one allele of Ly49G2 may express Ly49A from the same or opposite chromosome with equal likelihood, indicating that the expressed allele is chosen independently for different Ly49 genes. Finally, the data demonstrate that biallelic expression of Ly49A or Ly49G2 occurs least frequently in mice that express ligands for these receptors (H-2d mice), and most frequently in class I–deficient mice. Thus, biallelic expression of Ly49 genes is regulated by interactions of NK cell progenitors with MHC class I molecules

MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment

In MHC class I–deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self–major histocompatability complex (MHC) class I–specific inhibitory receptor, a process referred to as “licensing.” We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I–deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing