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- Allerbring, E. B., et al.
(författare)
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Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics
- 2012
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 42:11, s. 2990-3000
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Tidskriftsartikel (refereegranskat)abstract
- The molecular basis underlying T-cell recognition of MHC molecules presenting altered peptide ligands is still not wellestablished. A hierarchy of T-cell activation by MHC class I-restricted altered peptide ligands has been defined using the T-cell receptor P14 specific for H-2Db in complex with the immunodominant lymphocytic choriomeningitis virus peptide gp33 (KAVYNFATM). While substitution of tyrosine to phenylalanine (Y4F) or serine (Y4S) abolished recognition by P14, the TCR unexpectedly recognized H-2Db in complex with the alanine-substituted semiagonist Y4A, which displayed the most significant structural modification. The observed functional hierarchy gp33 > Y4A > Y4S = Y4F was neither due to higher stabilization capacity nor to differences in structural conformation. However, thermodynamic analysis demonstrated that while recognition of the full agonist H-2Db/gp33 was strictly enthalpy driven, recognition of the weak agonist H-2Db/Y4A was instead entropy driven with a large reduction in the favorable enthalpy term. The fourfold larger negative heat capacity derived for the interaction of P14 with H-2Db/gp33 compared with H-2Db/Y4A can possibly be explained by higher water entrapment at the TCR/MHC interface, which is also consistent with the measured opposite entropy contributions for the interactions of P14 with both MHCs. In conclusion, this study demonstrates that P14 makes use of different strategies to adapt to structural modifications in the MHC/peptide complex.
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- Demuth, Andreas, et al.
(författare)
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Pathogenomics: An updated European Research Agenda
- 2008
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-7257 .- 1567-1348. ; 8:3, s. 386-393
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Tidskriftsartikel (refereegranskat)abstract
- The emerging genomic technologies and bioinformatics provide novel opportunities for studying life-threatening human pathogens and to develop new applications for the improvement of human and animal health and the prevention, treatment, and diagnosis of infections. Based on the ecology and population biology of pathogens and related organisms and their connection to epidemiology, more accurate typing technologies and approaches will lead to better means of disease control. The analysis of the genome plasticity and gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs. The study of newly identified and uncultivated microorganisms enables the identification of new threats. The scrutiny of the metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches. The development of modulators of host responses and mediators of host damage will be facilitated by the research on interactions of microbes and hosts, including mechanisms of host damage, acute and chronic relationships as well as commensalisms. The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions. Needless to iterate, the application of the results of improved prevention and treatment of infections into clinical tests will have a positive impact on the management of human and animal disease. The Pathogenomics Research Agenda draws on discussions with experts of the Network of Excellence "EuroPathoGenomics" at the management board meeting of the project held during 18-21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the meeting's participants updated the established list of topics as the research agenda for the future.
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- Erkers, T, et al.
(författare)
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Lymphocytes in Placental Tissues: Immune Regulation and Translational Possibilities for Immunotherapy
- 2017
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2017, s. 5738371-
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Tidskriftsartikel (refereegranskat)abstract
- Immune modulation at the fetomaternal interface is crucial to ensure that the fetal allograft is not rejected. In the present review, the focus is to describe basic functions of lymphocyte populations and how they may contribute to fetomaternal immune regulation, as well as determining what proportions and effector functions of these cells are reported to be present in placental tissues in humans. Also explored is the possibility that unique cell populations at the fetomaternal interface may be targets for adoptive cell therapy. Increasing the understanding of immune modulation during pregnancy can give valuable insight into other established fields such as allogeneic hematopoietic stem cell transplantation and solid organ transplantation. In these settings, lymphocytes are key components that contribute to inflammation and rejection of either patient or donor tissues following transplantation. In contrast, an allogeneic fetus eludes rejection by the maternal immune system.
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- Jarmar, Tobias, et al.
(författare)
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Injectable bone cements for vertebroplasty studied in sheep vertebrae with electron microscopy
- 2008
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Ingår i: Key Engineering Materials. - 1662-9795.
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Tidskriftsartikel (refereegranskat)abstract
- Vertebral compression fractures were simulated by making a hole into sheep vertebrae and by injecting a stabilizing material. The injectable bio-ceramic Xeraspine™ was evaluated together with a commercially available PMMA (Vertebroplastic™) as the reference material. The Vertebrae were harvested after 7 days and prepared for microscopy. The samples were deposited with gold on the surface and thereafter subjected to SEM and EDX analysis. It was found that the Xeraspine-bone interface was composed of a mixture of elements. The Vertebroplastic implant was embedded in a carbon containing tissue, likely a soft tissue capsule. The Xeraspine sample was subjected to high resolution analysis in the TEM combined with EDX measurements. The TEM sample was prepared with a novel technique for preparation of the tissue-material interface (FIB). In the TEM analysis it was found that the interface region consists of ZrO2 together with a mixture possibly consisting of katoite and apatite formed during setting and/or originating from the boneapatite.
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