scholarly journals Molecular Characterization of MHC Class I Genes in Four Species of the Turdidae Family to Assess Genetic Diversity and Selection

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Muhammad Usman Ghani ◽  
Li Bo ◽  
An Buyang ◽  
Xu Yanchun ◽  
Shakeel Hussain ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mhc Class I ◽  
Gene Diversity ◽  
Geographical Area ◽  
Class I ◽  
Mhc I ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
I Gene

In vertebrate animals, the molecules encoded by major histocompatibility complex (MHC) genes play an essential role in the adaptive immunity. MHC class I deals with intracellular pathogens (virus) in birds. MHC class I diversity depends on the consequence of local and global environment selective pressure and gene flow. Here, we evaluated the MHC class I gene in four species of the Turdidae family from a broad geographical area of northeast China. We isolated 77 MHC class I sequences, including 47 putatively functional sequences and 30 pseudosequences from 80 individuals. Using the method based on analysis of cloned amplicons ( n = 25 ) for each species, we found two and seven MHC I sequences per individual indicating more than one MHC I locus identified in all sampled species. Results revealed an overall elevated genetic diversity at MHC class I, evidence of different selection patterns among the domains of PBR and non-PBR. Alleles are found to be divergent with overall polymorphic sites per species ranging between 58 and 70 (out of 291 sites). Moreover, transspecies alleles were evident due to convergent evolution or recent speciation for the genus. Phylogenetic relationships among MHC I show an intermingling of alleles clustering among the Turdidae family rather than between other passerines. Pronounced MHC I gene diversity is essential for the existence of species. Our study signifies a valuable tool for the characterization of evolutionary relevant difference across a population of birds with high conservational concerns.

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

scholarly journals The MHC class I peptide repertoire is molded by the transcriptome

2008 ◽  
Vol 205 (3) ◽  
pp. 595-610 ◽  
Author(s):  
Marie-Hélène Fortier ◽  
Étienne Caron ◽  
Marie-Pierre Hardy ◽  
Grégory Voisin ◽  
Sébastien Lemieux ◽  
...  
Keyword(s):  
Mhc Class I ◽  
High Throughput ◽  
Class I ◽  
High Throughput Analysis ◽  
Mhc I ◽  
Cyclin Dependent Kinases ◽  
Histocompatibility Complex ◽  
Accurate Definition ◽  
Primary Mouse ◽  
Definition Of

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.

scholarly journals Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells

2006 ◽  
Vol 189 (3) ◽  
pp. 605-615 ◽  
Author(s):  
C Giuliani ◽  
M Saji ◽  
I Bucci ◽  
G Fiore ◽  
M Liberatore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Promoter Activity ◽  
Class I ◽  
Thyroid Cells ◽  
Histocompatibility Complex ◽  
Igf I ◽  
I Gene ◽  
Mhc Class I Gene

Increased major histocompatibility complex (MHC) class I gene expression in nonimmune cell ‘target tissues’ involved in organ-specific diseases may be important in the pathogenesis of autoimmune diseases. This possibility in part evolves from studies of cultured thyrocytes where properties appear relevant to the development of thyroid autoimmune disease. In FRTL-5 rat thyroid cells in continuous culture, hormones and growth factors that regulate cell growth and function specifically decrease MHC class I gene expression. We hypothesized that this could reflect a mechanism to preserve self-tolerance and prevent autoimmune disease. The mechanisms of action of some of these hormones, namely TSH and hydrocortisone, have been already characterized. In this report, we show that IGF-I transcriptionally downregulates MHC class I gene expression and that its action is similar to that of insulin. The two hormones have a complex effect on the promoter of the MHC class I gene, PD1. In fact, they decrease the full promoter activity, but upregulate the activity of deleted mutants that have lost an upstream, tissue-specific regulatory region but still retain the enhancer A region. We show that insulin/IGF-I promotes the interactions of the p50/p65 subunits of NF-κB and AP-1 family members with these two regions, and that the tissue-specific region acts as a dominant silencer element on insulin/IGF-I regulation of promoter activity. These observations may be important to understand how MHC class I gene transcription is regulated in the cells.

scholarly journals Immunopeptidomics for Dummies: Detailed Experimental Protocols and Rapid, User-Friendly Visualization of MHC I and II Ligand Datasets with MhcVizPipe

2020 ◽  
Author(s):  
Kevin A. Kovalchik ◽  
Laura Wessling ◽  
Frederic Saab ◽  
Qing Ma ◽  
Jérôme Despault ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Software Tool ◽  
Class I ◽  
Mhc I ◽  
Binding Motifs ◽  
Histocompatibility Complex ◽  
Starting Point ◽  
Technical Report ◽  
Experimental Protocols ◽  
User Friendly

ABSTRACTImmunopeptidomics refers to the science of investigating the composition and dynamics of peptides presented by major histocompatibility complex (MHC) class I and class II molecules using mass spectrometry (MS). Here, we aim to provide a technical report to any non-expert in the field wishing to establish and/or optimize an immunopeptidomic workflow with relatively limited computational knowledge and resources. To this end, we thoroughly describe step-by-step instructions to isolate MHC class I and II-associated peptides from various biological sources, including mouse and human biospecimens. Most notably, we created MhcVizPipe (MVP) (https://github.com/CaronLab/MhcVizPipe), a new and easy-to-use open-source software tool to rapidly assess the quality and the specific enrichment of immunopeptidomic datasets upon the establishment of new workflows. In fact, MVP enables intuitive visualization of multiple immunopeptidomic datasets upon testing sample preparation protocols and new antibodies for the isolation of MHC class I and II peptides. In addition, MVP enables the identification of unexpected binding motifs and facilitates the analysis of non-canonical MHC peptides. We anticipate that the experimental and bioinformatic resources provided herein will represent a great starting point for any non-expert and will therefore foster the accessibility and expansion of the field to ultimately boost its maturity and impact.

Haplotype characterization of transcribed ovine major histocompatibility complex (MHC) class I genes

2005 ◽  
Vol 57 (7) ◽  
pp. 499-509 ◽  
Author(s):  
Despoina Miltiadou ◽  
Keith T. Ballingall ◽  
Shirley A. Ellis ◽  
George C. Russell ◽  
Declan J. McKeever
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

1991 ◽  
Vol 11 (8) ◽  
pp. 4217-4227 ◽  
Author(s):  
J D Weissman ◽  
D S Singer
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Dna Sequence ◽  
Regulatory Element ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
I Gene ◽  
Mhc Class I Gene

A novel regulatory element which contributes to the regulation of quantitative, tissue-specific differences in gene expression has been found between -771 and -676 bp upstream of the major histocompatibility complex (MHC) class I gene, PD1. Molecular dissection of this element reveals the presence of two overlapping functional activities: an enhancer and a silencer. Distinct nuclear factors bind to the overlapping enhancer and silencer DNA sequence elements within the regulatory domain. The levels of factors binding the silencer DNA sequence in different cell types are inversely related to levels of class I expression; in contrast, factors binding the enhancer DNA sequence can be detected in all cells. In cultured cell lines, inhibition of protein synthesis leads to the rapid loss of silencer complexes, with a concomitant increase in both enhancer complexes and MHC class I RNA. From these data, we conclude that a labile silencer factor competes with a constitutively expressed, stable enhancer factor for overlapping DNA-binding sites; the relative abundance of the silencer factor contributes to establishing steady-state levels of MHC class I gene expression.

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