PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9209515

Major histocompatibility complex-controlled protective influences on experimental autoimmune encephalomyelitis are peptide specific.

S Issazadeh·P Kjellén·T Olsson·M Mustafa·R Holmdahl
View original source ↗Export metadata ↓

Abstract

The myelin basic protein (MBP) peptide 63-88-induced experimental autoimmune encephalomyelitis (EAE) and its associated T cell cytokine profile are influenced by the rat major histocompatibility complex (MHC). There is an allele-specific protective influence of the MHC class I region, whereas the MHC class II region display either disease-protective or -promoting effects. To investigate if the MHC-associated protection is dependent on certain combinations of MBP peptide and MHC molecules, we have now used another peptide (MBP 89-101). A broader and different set of rat MHC alleles were associated with EAE induced with MBP 89-101 as compared to MBP 63-88. All EAE-susceptible strains mounted peptide-specific strong T helper (Th) 1-like immune responses in vitro. Immunization of rats with an extended peptide (MBP 87-110) induced EAE associated with the same MHC haplotypes as the 89-101 peptide, except in LEW.1N (RT1 pi) rats which were relatively resistant. Only this strain responded with additional Th2-like and transforming growth factor-beta responses to the peptide in vitro. In vivo depletion of CD8+ cells aggravated the disease in this strain. We conclude that both MHC-controlled promoting and protective influences on EAE are dependent on certain MHC/MBP peptide combinations, and that the 87-110 region of MBP contains a major MHC-associated encephalitogenic epitope in the rat.

Explore related subjects

AllelesAmino Acid SequenceAnimalsDisease SusceptibilityEncephalomyelitis, Autoimmune, ExperimentalEpitope MappingEpitopesImmunodominant EpitopesMajor Histocompatibility ComplexMolecular Sequence DataMyelin Basic ProteinPeptide FragmentsRatsRats, Inbred LewJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Issazadeh, P Kjellén, T Olsson, M Mustafa, R Holmdahl. 1997. Major histocompatibility complex-controlled protective influences on experimental autoimmune encephalomyelitis are peptide specific.. https://doi.org/10.1002/eji.1830270640

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

A de novo algorithm for allele reconstruction from Oxford nanopore amplicon reads, with application to CYP2D6.

MOTIVATION: The Oxford Nanopore Technologies' sequencing platform offers a path towards bedside genomics, producing long reads that can completely cover a gene of interest, and detect any known or novel variant the gene contains. However, the analysis of these long reads to identify actionable genotypes remains challenging and typically requires customization depending on the target gene. RESULTS: Here, we describe a generic algorithm to accurately reconstruct allele sequences derived from long-reads of amplicon-based data. Rather than calling variants directly from these long-reads, our method takes a "sequence-first" approach, performing an unbiased reconstruction of the underlying amplicon sequences to generate high-confidence reconstructed allele sequences. This is done without user input of the target gene, allowing for any source amplicon to be reconstructed. These high-confidence reconstructed allele sequences are then compared to the genomic reference sequence of the gene to infer the specific diplotype present in the sample. This approach is agnostic towards the number of genes and alleles present and readily detects novel variants. We demonstrate our approach using three independent data sets for CYP2D6, a diverse and complex gene with over 175 known alleles of clinical significance. We show how our approach can accurately recover validated CYP2D6 diplotypes from 20 Coriell samples covering 14 distinct alleles, using different amplicons, flow cell versions, and depths. This includes inferring occurrences of allele duplication events from relative abundances of each allele, a critical factor for ascribing functional effects to a diplotype. Further, we demonstrate our approach's utility for other genomic regions, including HLA. AVAILABILITY: Custom code is available at the following GitHub repository, along with instructions for use and test data: https://github.com/scottdbrown/allele-reconstruction-long-read-amplicon-data. A snapshot of the code at the time of publication is available on Zenodo.org; doi 10.5281/zenodo.19716004. Raw .fastq sequence data for our three sequencing runs is available at the SRA under Bioproject PRJNA1357883 (https://www.ncbi.nlm.nih.gov/bioproject/1357883).

Alleles↗
PubMed2026

Supergene control of chiral development in mirror-image flowers.

How genes determine the development of chiral structures is a fascinating question. The reciprocal placement of female and male organs on opposite sides of mirror-image flowers promotes efficient cross-pollination. Here, we identified that in butterfly lilies, female and male organs deflect by a combination of genetically controlled chirality and gravitropism, orienting left and right with respect to an external rather than internal reference axis. We found coordinated organ placement to be controlled by a hemizygous supergene containing two candidate causal loci, MIR156-R and YUCCA-R, that are responsible for opposite female and male organ orientation, respectively. The resulting differential placement of pollen carrying the two supergene alleles on pollinators' bodies leads to their transfer to the stigmas of flowers with opposite handedness and maintenance of the reproductive polymorphism.

Alleles↗
PubMed2026

DirectASRM: uncovering allele-specific post-transcriptional RNA modifications through direct RNA sequencing.

SUMMARY: We developed DirectASRM, a comprehensive database for the systematic identification, integration, and annotation of allele-specific RNA modifications (ASRMs) from direct RNA sequencing data. DirectASRM enables single-base, transcript-level detection of ASRMs across multiple RNA modification types, diverse organisms and condition-specific contexts. The database further evaluates the confidence of each ASRM-SNP pair association within isoform context by jointly considering statistical evidence of allelic modification imbalance and independent support from external next-generation sequencing (NGS) - based RNA modification resources. DirectASRM also provides extensive functional annotations for ASRMs and their associated variants, including intra-sample transcript-level allele-specific expression (ASE) and allele-specific splicing, as well as additional post-transcriptional regulatory features such as miRNA binding, circRNA, RNA-protein interactions, and disease relevance. Overall, DirectASRM serves as a comprehensive resource that supports systematic investigation of the potential functional impact of genetic variants in epitranscriptomic regulation. AVAILABILITY AND IMPLEMENTATION: DirectASRM database is freely accessible at http://modinfor.com/DirectASRM/. DirectASRM pipeline is available at GitHub (https://github.com/jiayin1101/DirectASRM_pipeline) and Zenodo (DOI: https://doi.org/10.5281/zenodo.19876077).

Alleles↗