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

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)

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

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

Die Innsbrucker Politikwissenschaft: Konsolidierung und Profilbildung

Der Beitrag gibt einen Überblick über die Etablierung und fachliche Profilbildung des Innsbrucker Instituts für Politikwissenschaft. Nach einem Rückblick auf die strukturellen und institutionellen Probleme der Pionierphase, die durch verknappte Ressourcen, curriculare Beschränkungen und einen organisatorischen Sonderstatus durch die Anbindung an zwei Fakultäten gekennzeichnet war, analysiert der Beitrag die Entwicklung der personellen Kapazitäten am Institut, die steigenden Studierenden- und AbsolventInnenzahlen wie die fortschreitende Ausdifferenzierung der Studienangebote als Konsequenz des Bologna-Prozesses. Zentrale Forschungsschwerpunkte der InstitutsmitarbeiterInnen, der graduelle Wandel der Forschungs- und Publikationskultur wie die internationale Vernetzung vor dem Hintergrund der fortschreitenden Europäisierung der Disziplin werden im Kontext analysiert und evaluiert

Differential tumor surveillance by natural killer (NK) and NKT cells

Natural tumor surveillance capabilities of the host were investigated in six different mouse tumor models where endogenous interleukin (IL)-12. does or does not dictate the efficiency of the innate immune response. Gene-targeted and lymphocyte subset-depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1(+) T (NKT) cells in protection from tumor initiation and metastasis. In the models examined, CD3(-) NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I-deficient tumors was independent of IL-12, A protective role for NKT cells was only observed when tumor rejection required endogenous IL-12 activity. In particular, T cell receptor J alpha 281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide

Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies

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