Based on analysis of available genome sequences, five gene lineages of MHC class I molecules (MHC I-U, -Z, -S, -L and -P) and one gene lineage of MHC class II molecules (MHC II-D) have been identified in Osteichthyes. In the latter lineage, three MHC II molecule sublineages have been identified (MHC II-A, -B and -E). As regards MHC class I molecules in Osteichthyes, it is important to take note of the fact that the lineages U and Z in MHC I genes have been identified in almost all fish species examined so far. Phylogenetic studies into MHC II molecule genes of sublineages A and B suggest that they may be descended from the genes of the sublineage named A/B that have been identified in spotted gar (). The sublineage E genes of MHC II molecules, which represent the group of non-polymorphic genes with poor expression in the tissues connected with the immune system, are present in primitive fish, . in paddlefish, sturgeons and spotted gar (), as well as in cyprinids (), Atlantic salmon (), and rainbow trout (). Full elucidation of the details relating to the organisation and functioning of the particular components of the major histocompatibility complex in Osteichthyes can advance the understanding of the evolution of the MHC molecule genes and the immune mechanism.
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http://dx.doi.org/10.2478/jvetres-2020-0025 | DOI Listing |
Clin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
View Article and Find Full Text PDFNat Cancer
January 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.
View Article and Find Full Text PDFCancer Cell
January 2025
Cancer Systems Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Centre for Cancer Evolution, Bart's Cancer Institute, Queen Mary University London, London EC1M 6AU, UK. Electronic address:
Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.
View Article and Find Full Text PDFImmunogenetics
January 2025
Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
T cells recognize peptides displayed on the surface of cells on MHC molecules. Genetic variation in MHC genes alters their peptide-binding repertoire and thus influences the potential immune response generated against pathogens. Both gorillas and chimpanzees show reduced diversity at their MHC class I A (MHC-A) locus compared to humans, which has been suggested to be the result of a pathogen-mediated selective sweep.
View Article and Find Full Text PDFCell Death Dis
January 2025
Department of Pathology, The Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
Approximately 80% of nasopharyngeal carcinoma (NPC) patients exhibit EGFR overexpression. The overexpression of EGFR has been linked to its potential role in modulating major histocompatibility complex class I (MHC-I) molecules. We discovered that EGFR, operating in a kinase-independent manner, played a role in stabilizing the expression of SLC7A11, which subsequently inhibited MHC-I antigen presentation.
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