Immunogenetics最新文献

{"title":"Histocompatibility in Botryllus schlosseri and the origins of adaptive immunity.","authors":"Anthony W De Tomaso, Henry Rodriguez-Valbuena","doi":"10.1007/s00251-025-01379-7","DOIUrl":"10.1007/s00251-025-01379-7","url":null,"abstract":"<p><p>The basal chordate, Botryllus schlosseri, undergoes a natural transplantation reaction that is controlled by a single, highly polymorphic locus called the fuhc. The fuhc is one of the most polymorphic loci ever described, with most populations having hundreds of alleles, and up to a thousand found worldwide. Two individuals are compatible if they share one or both alleles, while those with no shared alleles are incompatible; thus, Botryllus uses a missing-self recognition strategy to discriminate between up to a thousand histocompatibility ligands. Remarkably, this discriminatory capability, which rivals that of vertebrate adaptive immunity, is carried out by germline-encoded receptors; thus, the mechanisms that establish and maintain this remarkable specificity are not understood. Multiple complete haplotypes of the fuhc locus have recently been sequenced, and at least seven genes with characteristics that suggest a role in allorecognition have been identified, including ligands, receptors, and intracellular proteins that likely organize and tune signal transduction complexes. This includes a new receptor family called the fester co-receptors (FcoRs) that encode ITIM and hemITAM domains, linking allorecognition in Botryllus to canonical immune transduction pathways. This review will summarize our current understanding and working hypotheses on the cellular and molecular mechanisms that control this innate, highly polymorphic allorecognition response, and how those may have been co-opted during the evolution of adaptive immunity.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"22"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide diversity and MHC characterisation in a critically endangered freshwater turtle susceptible to disease.","authors":"Holly V Nelson, Luke Silver, Toby G L Kovacs, Elspeth A McLennan, Arthur Georges, Jane L DeGabriel, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-025-01378-8","DOIUrl":"https://doi.org/10.1007/s00251-025-01378-8","url":null,"abstract":"<p><p>Small, isolated populations are often vulnerable to increased inbreeding and genetic drift, both of which elevate the risk of extinction. The Bellinger River turtle (Myuchelys georgesi) is a critically endangered species endemic to a single river catchment in New South Wales, Australia. The only extant wild population, along with the breeding program, face significant threats from viral outbreaks, most notably a nidovirus outbreak in 2015 that led to a 90% population decline. To enhance our understanding of genomic characteristics in the species, including genome-wide and functional gene diversity, we re-sequenced, assembled, and analysed 31 re-sequenced genomes for pure M. georgesi (N = 31). We manually annotated the major histocompatibility complex (MHC), identifying five MHC class I and ten MHC class II genes and investigated genetic diversity across both classes in M. georgesi. Our results showed that genome-wide diversity is critically low in pure M. georgesi, contexualised through comparison with opportunistically sampled backcross animals-offspring of F1 hybrids (M. georgesi × Emydura macquarii) backcrossed to pure M. georgesi (N = 4). However, the variation observed within the core MHC region of pure M. georgesi, extending across scaffold 10, exceeded that of all other macrochromosomes. Additionally, no significant short-term changes in either genome-wide or immunogenetic diversity were detected following the 2015 nidovirus outbreak (before; N = 19, after; N = 12). Demographic history reconstructions indicated a sustained, long-term decline in effective population size since the last interglacial period, accompanied by more recent steep declines. These patterns suggested that prolonged isolation and reduced population size have significantly influenced the dynamics of genome-wide diversity. It is likely that contemporary stressors, including the recent nidovirus outbreak, are acting on an already genetically depleted population. This study offers new insights into genome-wide and immune gene diversity, including immune gene annotation data with broader implications for testudines. These findings provide crucial information to support future management strategies for the species.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"21"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: HCV immunodominant peptide mapping reveals unique HLA‑A* 02‑restricted signatures: insights for CD8⁺ T‑cell‑based vaccines and immunotherapies.","authors":"Laura Cardoso Corrêa-Dias, Ágata Lopes-Ribeiro, Geovane Marques-Ferreira, Letícia Gomes-de-Pontes, Thaiza Aline Pereira-Santos, Erik Vinicius de Sousa Reis, Thaís de Fátima Silva Moraes, Olindo Assis Martins-Filho, Edel Figueiredo Barbosa-Stancioli, Flávio Guimarães da Fonseca, Jordana Grazziela Coelho-Dos-Reis","doi":"10.1007/s00251-025-01377-9","DOIUrl":"https://doi.org/10.1007/s00251-025-01377-9","url":null,"abstract":"","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"20"},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allele co-segregation and haplotype diversity of MHC IIβ genes in the small-spotted catshark Scyliorhinus canicula.","authors":"Alessia Rota, Ana Veríssimo, Arnaud Gaigher","doi":"10.1007/s00251-025-01376-w","DOIUrl":"10.1007/s00251-025-01376-w","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) constitutes a functionally relevant multigene family playing an essential role in the adaptive immune responses of jawed vertebrates, being directly involved in pathogen recognition. MHC diversity, driven by pathogen-mediated selection, is vital for species survival and is characterized by high genetic diversity in many taxa, namely at the sequence, allelic and haplotype levels. Chondrichthyans, the most basal jawed vertebrates with an adaptive immune system, exhibit a high diversity of MHC gene lineages conservatively organized in a compact region of the genome. Such genomic architecture suggests linkage among MHC genes, where alleles from different genes possibly co-segregate together. Such condition may have major implications on immune response, individual fitness and evolution. In this study, we examine MHC IIβ haplotype diversity in a model shark species, the small spotted catshark, Scyliorhinus canicula. Making use of pedigree data, we reconstructed MHC IIβ haplotypes to understand allele transmission from parent to offspring. Results indicate allele co-segregation consistent with tight linkage among MHC IIβ genes, suggesting the presence of functional stable haplotypes inherited from parents to offspring. The reconstructed haplotypes suggested extensive haplotype diversity characterized by variable allele numbers and allelic lineage composition, as well as marked allelic divergence, consistent with previous population-level data on this species. These findings underscore the complexity of MHC genetics (and of MHC evolution) in chondrichthyans. Accurate reconstruction of MHC haplotypes and assessment of its functional significance are crucial for better understanding adaptive immune responses and MHC evolutionary dynamics in chondrichthyans.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"19"},"PeriodicalIF":2.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates.","authors":"Taiki Ito, Carla Guenther, Eri Ishikawa, Takae Yabuki, Masamichi Nagae, Yoichiro Nakatani, Sho Yamasaki","doi":"10.1007/s00251-025-01375-x","DOIUrl":"10.1007/s00251-025-01375-x","url":null,"abstract":"<p><p>Our bodies are continuously exposed to injurious insults by infection and tissue damage, which are primarily sensed by innate immune receptors to maintain homeostasis. Among such receptors is macrophage-inducible C-type lectin (Mincle, gene symbol CLEC4E), a member of the C-type lectin receptor (CLR) family, which functions as an immune sensor for both pathogens and damaged self. To monitor these injurious stimuli, Mincle recognizes disaccharide-based pathogen-derived glycolipids and monosaccharide-based intracellular metabolites, such as β-glucosylceramide. Mincle is well-conserved among mammals; however, there are questions that remain unclear, such as from which lower vertebrate did it arise and whether the original ligand was self or non-self. Here, we found homologues of Mincle and its signaling subunit Fc receptor γ chain (FcRγ) in lower vertebrates, such as reptiles, amphibians, and fishes. The crystal structure of a Mincle homologue revealed that fish Mincle possesses a narrower sugar-binding pocket than that of mammalian Mincle, and accommodates only monosaccharide moieties. These results suggest that Mincle may have evolved from a self-recognizing receptor, and its sugar-binding pocket widened during evolution, presumably to adapt to disaccharide-based glycolipids derived from life-threatening pathogens.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"18"},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kirsten Falk 1963-2024.","authors":"Hans-Georg Rammensee, Olaf Rötzschke","doi":"10.1007/s00251-025-01373-z","DOIUrl":"10.1007/s00251-025-01373-z","url":null,"abstract":"","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"17"},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppressed activation of the IRF7 and TLR9 by JAK2V617F gold nanoparticles.","authors":"Berkay Tokcan, Esra Nur Demirtaş, Selçuk Sözer","doi":"10.1007/s00251-025-01374-y","DOIUrl":"10.1007/s00251-025-01374-y","url":null,"abstract":"<p><p>Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are characterized by the overproduction of myeloid cells and a lack of response to cytokine signaling, along with genomic instability and the accumulation of nucleic acids in the cytoplasm. In this study, we investigated the effects of oligonucleotide-gold nanoparticle conjugates (ON-GNPs) targeting JAK2 or JAK2V617F mRNAs on nucleic acid-sensing pathways in HEL, SET2, and K562 cell lines. We evaluated changes in gene expression related to TLR9 and cGAS/STING pathways, RAGE/TLR9 receptor dynamics, and inflammatory cytokine release over short-term (0.5-2 h) and long-term (24-72 h) exposures. Our results demonstrated that ON-GNPs transiently suppressed TLR9, IRF7, and NFKB1 expression during the short term, followed by significant upregulation after 24 h, persisting up to 72 h. Notably, JAK2V617F-targeting ON-GNPs induced heightened IRF7 activation in HEL and SET2 cells after 24 h without affecting TLR9/RAGE expression. Additionally, IL-8 secretion increased in HEL and SET2 culture media after 72 h, correlating with interferon pathway activation. This study reveals that complementary ON-GNPs can modulate nucleic acid-sensing pathways, suppressing IL-8 and inflammatory signaling in the short term while inducing delayed activation of TLR9 and IRF7 in the presence of JAK2V617F. These findings provide a promising foundation for developing ON-GNP-based therapeutic strategies to manage inflammation and disease progression in Ph-MPNs.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"16"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary regulatory T cell activator FOXP3 is present across Amphibia.","authors":"Rebecca A Clemons, Chase H Smith, Kelly R Zamudio","doi":"10.1007/s00251-025-01372-0","DOIUrl":"10.1007/s00251-025-01372-0","url":null,"abstract":"<p><p>The overall structure of the immune system is highly conserved across jawed vertebrates, but characterization and description of the immune system is heavily biased toward mammals. One arm of the vertebrate immune system, the adaptive immune system, mounts pathogen-specific responses that tend to be robust and effective at clearing pathogens. This system requires selection against self-recognition and modulation of the immune response. One of the mechanisms of immune modulation is the presence of regulatory T cells that suppress other effector immune cells. Regulatory T cells and their primary activator forkhead box protein P3 (FOXP3) have been well characterized in mammalian models but unexplored in most other vertebrate taxa. Amphibians are a good focal group for the characterization of FOXP3 due to their phylogenetic position on the vertebrate tree of life, and their susceptibility to emerging pathogens. In this study, we mined available transcriptomic and genomic data to confirm the presence of FOXP3 across the amphibian tree of life. We find that FOXP3 is present in all major clades of amphibians. We also test whether selection on FOXP3 shows signatures of intensification among the three main clades of amphibians, which may reflect shifts in the stringency of natural selection on this gene. Our findings provide insights into the evolutionary history of the vertebrate immune system and confirm the conservation of vertebrate immune genes within amphibians.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"15"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Full-length mRNA sequencing resolves novel variation in 5' UTR length for genes expressed during human CD4 T-cell activation.","authors":"Cassandra R Woolley, Julia H Chariker, Eric C Rouchka, Easton E Ford, Elizabeth Hudson, Kamille M Rasche, Caleb S Whitley, Zachary Vanwinkle, Carolyn R Casella, Melissa L Smith, Thomas C Mitchell","doi":"10.1007/s00251-025-01371-1","DOIUrl":"10.1007/s00251-025-01371-1","url":null,"abstract":"<p><p>Isoform sequencing (Iso-Seq) uses long-read technology to produce highly accurate full-length reads of mRNA transcripts. Visualization of individual mRNA molecules can reveal new details of transcript variation within understudied portions of mRNA, such as the 5' untranslated region (UTR). Differential 5' UTRs may contain motifs, upstream open reading frames (uORFs), and secondary structures that can serve to regulate translation or further indicate changes in promoter usage, where transcriptional control may impact protein expression levels. To begin to explore isoform variation during T-cell activation, we generated the first Iso-Seq reference transcriptome of activated human CD4 T cells. Within this dataset, we discovered many novel splice- and end-variant transcripts. Remarkably, one in every eight genes expressed in our dataset was found to have a notable proportion of transcripts with 5' UTR lengthened by over 100 bp compared to the longest corresponding UTR within the Gencode dataset. Among these end-variant transcripts, two novel isoforms were identified for CXCR5, a chemokine receptor associated with T follicular helper cell (Tfh) function and differentiation. When investigated in a model cell system, these lengthened UTR conferred reduced transcript stability and, for one of these isoforms, short uORFs introduced by the added length altered protein expression kinetics. This study highlights instances in which current reference databases are incomplete relative to the information obtained by long-read sequencing of intact mRNA. Iso-Seq is thus a promising approach to better understanding the plasticity of promoter usage, alternative splicing, and UTR sequences that influence RNA stability and translation efficiency.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"14"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCV immunodominant peptide mapping reveals unique HLA-A*02-restricted signatures: insights for CD8⁺ T-cell-based vaccines and immunotherapies.","authors":"Laura Cardoso Corrêa-Dias, Ágata Lopes-Ribeiro, Geovane Marques-Ferreira, Letícia Gomes-de-Pontes, Thaiza Aline Pereira-Santos, Erik Vinicius de Sousa Reis, Thaís de Fátima Silva Moraes, Olindo Assis Martins-Filho, Edel Figueiredo Barbosa-Stancioli, Flávio Guimarães da Fonseca, Jordana Grazziela Coelho-Dos-Reis","doi":"10.1007/s00251-025-01370-2","DOIUrl":"10.1007/s00251-025-01370-2","url":null,"abstract":"<p><p>Several barriers for the development of an HCV vaccine still exist, including the genetic diversity of the virus, and the shortage of assessable models for in vitro and in vivo assays. Therefore, in this study, HCV epitope mapping was performed for 59 polyprotein sequences from 7 HCV genotypes. Around 2,880 peptides were considered epitopes for CD8⁺ T cells. The peptide induction of cytokines from Th1 and/or Th2 axes of the cellular immune response was assessed, indicating a tendency for Th2 axis. In vitro evaluation was performed using peptide microarray and a recombinant HLA-A*02:01 molecule. A total of 615 peptides of high reactivity to HLA-A*02:01 were identified, with predominance of leucine and tryptophan residues, highlighting their importance for TCR-epitope binding and CD8⁺ T activation. Finally, HCV-derived peptide patterns restricted to HLA-A2*02:01 observed in this study provide important information for the development of a multi-epitope-based pan-genotypic vaccine against the virus.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"13"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}