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Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing.
Front Genet
October 2022
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Inborn errors of immunity are known to influence susceptibility to mycobacterial infections. The aim of this study was to characterize the genetic profile of nine patients with mycobacterial infections (eight with BCGitis and one with disseminated tuberculosis) from the Republic of Moldova using whole-exome sequencing. In total, 12 variants in eight genes known to be associated with Mendelian Susceptibility to Mycobacterial Disease (MSMD) were detected in six out of nine patients examined.
View Article and Find Full Text PDFImmunology according to Dembic: Preserving integrity is key.
Scand J Immunol
May 2022
Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Stockholm, Sweden.
Regulatory T cells and co-evolution of allele-specific MHC recognition by the TCR.
Scand J Immunol
March 2020
GMDxCo Pty Ltd, Melbourne, Vic, Australia.
What is the evolutionary mechanism for the TCR-MHC-conserved interaction? We extend Dembic's model (Dembic Z. In, Scand J Immunol e12806, 2019) of thymus positive selection for high-avidity anti-self-MHC Tregs among double (CD4 + CD8+)-positive (DP) developing thymocytes. This model is based on competition for self-MHC (+ Pep) complexes presented on cortical epithelium.
View Article and Find Full Text PDFOn integrity in immunity during ontogeny or how thymic regulatory T cells work.
Scand J Immunol
November 2019
Department of Oral Biology, University of Oslo, Oslo, Norway.
The Standard model of T cell recognition asserts that T cell receptor (TCR) specificities are positively and negatively selected during ontogeny in the thymus and that peripheral T cell repertoire has mild self-major histocompatibility complex (MHC) reactivity, known as MHC restriction of foreign antigen. Thus, the TCR must bind both a restrictive molecule (MHC allele) and a peptide reclining in its groove (pMHC ligand) in order to transmit signal into a T cell. The Standard and Cohn's Tritope models suggest contradictory roles for complementarity-determining regions (CDRs) of the TCRs.
View Article and Find Full Text PDFThe case for allele-specific recognition by the TCR.
Scand J Immunol
August 2019
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
There is a sharp difference in how one views TCR structure-function-behaviour dependent on whether its recognition of major histocompatibility complex-encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele-specific. The establishing of allele-specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model.
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