Pathogens are increasingly emerging in human-altered environments as a serious threat to biodiversity. In this context of rapid environmental changes, improving our knowledge on the interaction between ecology and evolution is critical. The objective of this study was to evaluate the influence of an immunocompetence gene, the major histocompatibility complex (MHC) class IIbeta, on the pathogen infection levels in wild Atlantic salmon populations, Salmo salar, and identify selective agents involved in contemporary coevolution. MHC variability and bacterial infection rate were determined throughout the summer in juvenile salmon from six rivers belonging to different genetic and ecological regions in Québec, Canada. A total of 13 different pathogens were identified in kidney by DNA sequence analysis, including a predominant myxozoa, most probably recently introduced in North America. Infection rates were the highest in southern rivers at the beginning of the summer (average 47.6+/-6.3% infected fish). One MHC allele conferred a 2.9 times greater chance of being resistant to myxozoa, while another allele increased susceptibility by 3.4 times. The decrease in frequency of the susceptibility allele but not other MHC or microsatellite alleles during summer was suggestive of a mortality event from myxozoa infection. These results supported the hypothesis of pathogen-driven selection in the wild by means of frequency-dependent selection or change in selection through time and space rather than heterozygous advantage, and underline the importance of MHC standing genetic variation for facing pathogens in a changing environment.
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http://dx.doi.org/10.1098/rstb.2009.0011 | DOI Listing |
Nat Commun
January 2025
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.
The inherent antigen cross-reactivity of the T cell receptor (TCR) is balanced by high specificity. Surprisingly, TCR specificity often manifests in ways not easily interpreted from static structures. Here we show that TCR discrimination between an HLA-A*03:01 (HLA-A3)-restricted public neoantigen and its wild-type (WT) counterpart emerges from distinct motions within the HLA-A3 peptide binding groove that vary with the identity of the peptide's first primary anchor.
View Article and Find Full Text PDFJ Exp Med
January 2025
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ.
View Article and Find Full Text PDFAutoimmun Rev
September 2024
Department of Neurology and Translational Research Center (TRACE), Rigshospitalet, Nordstjernevej 42, DK-2600 Glostrup, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark. Electronic address:
Autoimmune diseases constitute a broad, heterogenous group with many diverse and often overlapping symptoms. Even so, they are traditionally classified as either systemic, rheumatic diseases or organ-directed diseases. Several theories exist about autoimmune diseases, including defective self-recognition, altered self, molecular mimicry, bystander activation and epitope spreading.
View Article and Find Full Text PDFVet World
June 2024
Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, United Arab Emirates.
Background And Aim: , with its diverse virulence factors and immune response evasion mechanisms, presents a formidable challenge as an opportunistic pathogen. Developing an effective vaccine against has proven elusive despite extensive efforts. Autologous lysate (ASL) treatment has proven effective in triggering an immune response against bovine mastitis.
View Article and Find Full Text PDFJ Allergy Clin Immunol Pract
September 2024
Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey. Electronic address:
Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored.
Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates.
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