scholarly journals Wetter climates select for higher immune gene diversity in resident, but not migratory, songbirds

2020 ◽  
Vol 287 (1919) ◽  
pp. 20192675 ◽  
Author(s):  
Emily A. O'Connor ◽  
Dennis Hasselquist ◽  
Jan-Åke Nilsson ◽  
Helena Westerdahl ◽  
Charlie K. Cornwallis
Keyword(s):  
Immune System ◽  
Gene Diversity ◽  
Immune Gene ◽  
Class I Mhc ◽  
Mhc I ◽  
Tropical Regions ◽  
Immune Genes ◽  
Histocompatibility Complex ◽  
Geographical Regions ◽  
Migratory Songbirds

Pathogen communities can vary substantially between geographical regions due to different environmental conditions. However, little is known about how host immune systems respond to environmental variation across macro-ecological and evolutionary scales. Here, we select 37 species of songbird that inhabit diverse environments, including African and Palaearctic residents and Afro-Palaearctic migrants, to address how climate and habitat have influenced the evolution of key immune genes, the major histocompatibility complex class I (MHC-I). Resident species living in wetter regions, especially in Africa, had higher MHC-I diversity than species living in drier regions, irrespective of the habitats they occupy. By contrast, no relationship was found between MHC-I diversity and precipitation in migrants. Our results suggest that the immune system of birds has evolved greater pathogen recognition in wetter tropical regions. Furthermore, evolving transcontinental migration appears to have enabled species to escape wet, pathogen-rich areas at key periods of the year, relaxing selection for diversity in immune genes and potentially reducing immune system costs.

Major histocompatibility complex class I (MHC 1) expression in clear cell renal cell carcinoma: Correlation with clinical outcome.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 541-541
Author(s):  
Viraj A. Master ◽  
Sarah Holzman ◽  
Brian Pollack ◽  
Adeboya O. Osunkoya
Keyword(s):  
Renal Cell Carcinoma ◽  
Immune System ◽  
Clear Cell ◽  
T Test ◽  
Complex Class ◽  
Cell Renal Cell Carcinoma ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

541 Background: Most patients with clear cell renal cell carcinoma (ccRCC) initially present with localized disease but a fraction subsequently develop metastases. Current predictive models of ccRCC recurrence are imperfect, suggesting a need for additional predictors. Metastatic ccRCC may be modulated by the immune system, suggesting that the immune system plays a role in tumor progression. Major histocompatibility complex class I (MHC I) expression on tumor cells is critical for immune system recognition. Here, we analyzed MHC I expression in ccRCC and its correlation with clinical outcomes. Methods: ccRCC patients who underwent radical nephrectomy with a ≥4 years of follow-up, without T4 disease or metastasis at presentation were included. All slides were re-reviewed by a single Urologic Pathologist and blocks with tumor and adjacent renal parenchyma were selected for each case for immunohistochemical staining for MHC I . Whole slide scanning and automated image analysis was used; representative areas of tumor and normal kidney were selected and averaged with Aperio image analysis software (positive pixel count v. 9). Unpaired t-test and one-way ANOVA were performed in GraphPad Prism. Results: 34 patients were analyzed. Fuhrman nuclear grades (FNG) were: FNG 2 10/34 (29%), FNG 3 20/34 (59%) and FNG 4 4/34 (11%). Although there was no correlation with FNG and MHC1 (ANOVA, p=0.800), patients who were alive at follow up had increased MHCI expression (80.1% average positivity score) than those who died (53% average positivity score; t-test, p<0.0001). Patients living with recurrence had increased MHCI expression (81.3% positivity score) compared to those who succumbed to their disease (53.2% positivity score; t-test, p<0.0001). Conclusions: MHCI expression may be an important prognostic factor in ccRCC for recurrence free survival, and also for prognosis of those patients with recurrence. This is the first study to show that increased MHCI expression is a favorable prognostic indicator in metastatic ccRCC. These results suggest that MHCI expression plays an important role in tumor-host immune system interaction of ccRCC and merits further study.

scholarly journals High MHC gene copy number maintains diversity despite homozygosity in a Critically Endangered single-island endemic bird, but no evidence of MHC-based mate choice

2020 ◽  
Author(s):  
Martin Stervander ◽  
Elisa G. Dierickx ◽  
Jack Thorley ◽  
M. de L. Brooke ◽  
Helena Westerdahl
Keyword(s):  
Mate Choice ◽  
Gene Diversity ◽  
Gene Copy Number ◽  
Small Population ◽  
Critically Endangered ◽  
Gene Copy ◽  
Immune Gene ◽  
Class I Mhc ◽  
Mhc I ◽  
Island Endemic

AbstractSmall population sizes can, over time, put species at risk due to the loss of genetic variation and the deleterious effects of inbreeding. Losing diversity in the major histocompatibility complex (MHC) could be particularly harmful, given its key role in the immune system. Here, we assess MHC class I (MHC-I) diversity and its effects on mate choice and survival in the Critically Endangered Raso lark Alauda razae, a species restricted to the 7 km2 islet of Raso (Cape Verde) since ~1460, whose population size has dropped as low as 20 pairs. Exhaustively genotyping 122 individuals, we find no effect of MHC-I genotype/diversity on mate choice or survival. However, we demonstrate that MHC-I diversity has been maintained through extreme bottlenecks by retention of a high number of gene copies (at least 14), aided by co-segregation of multiple haplotypes comprising 2–8 linked MHC-I loci. Within-locus homozygosity is high, contributing to comparably low population-wide diversity. Conversely, each individual had comparably many alleles, 6–16 (average 11), and the large and divergent haplotypes occur at high frequency in the population, resulting in high within-individual MHC-I diversity. This functional immune gene diversity will be of critical importance for this highly threatened species’ adaptive potential.

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 Bovine papillomavirus type 1 oncoprotein E5 inhibits equine MHC class I and interacts with equine MHC I heavy chain

2009 ◽  
Vol 90 (12) ◽  
pp. 2865-2870 ◽  
Author(s):  
Barbara Marchetti ◽  
Elisabeth A. Gault ◽  
Marc S. Cortese ◽  
ZhengQiang Yuan ◽  
Shirley A. Ellis ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Class I ◽  
Bovine Papillomavirus ◽  
Class I Mhc ◽  
Mhc I ◽  
Reading Frame ◽  
Histocompatibility Complex ◽  
Human Telomerase

Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 cells were morphologically transformed, elongated with many pseudopodia and capable of forming foci. Equine major histocompatibility complex class I (MHC I) was inhibited in these cells at least at two levels: transcription of MHC I heavy chain was inhibited and the MHC I complex was retained in the Golgi apparatus and prevented from reaching the cell surface. We conclude that, as in bovine cells and tumours, E5 is a player in the transformation of equine cells and the induction of sarcoids, and a potential major cause of MHC I downregulation and hence poor immune clearance of tumour cells.

scholarly journals Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes

2022 ◽  
Vol 12 ◽  
Author(s):  
Richèl J. C. Bilderbeek ◽  
Maksim V. Baranov ◽  
Geert van den Bogaart ◽  
Frans Bianchi
Keyword(s):  
T Cell ◽  
Membrane Proteins ◽  
T Cell Responses ◽  
Class I ◽  
Complex Class ◽  
Transmembrane Helices ◽  
Class I Mhc ◽  
Mhc I ◽  
Cell Responses ◽  
Histocompatibility Complex

Cytolytic T cell responses are predicted to be biased towards membrane proteins. The peptide-binding grooves of most alleles of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefore peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often as would be expected based on their abundance in the proteome. However, the physiological reason of why membrane proteins might be over-presented is unclear. In this study, we show that the predicted over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses and for both MHC-I and MHC-II, and confirmed by re-analysis of epitope databases. Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions. Thus, our findings suggest that both cytolytic and helper T cells are more tuned to respond to membrane proteins, because these are evolutionary more conserved. We speculate that TMHs are less prone to mutations that enable pathogens to evade T cell responses.

scholarly journals Transmembrane helices are an overlooked and evolutionarily conserved source of major histocompatibility complex class II epitopes

2021 ◽  
Author(s):  
Richel Bilderbeek ◽  
Maksim Baranov ◽  
Frans Bianchi ◽  
Geert van den Bogaart
Keyword(s):  
T Cell ◽  
Membrane Proteins ◽  
T Cell Responses ◽  
Nucleotide Polymorphisms ◽  
Complex Class ◽  
Transmembrane Helices ◽  
Class I Mhc ◽  
Mhc I ◽  
Cell Responses ◽  
Histocompatibility Complex

Cytolytic T cell responses are predicted to be biased towards membrane proteins. The peptide-binding grooves of most haplotypes of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefor peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often as would be expected based on their abundance in the proteome. However, the physiological reason of why membrane proteins might be over-presented is unclear. In this study, we show that the over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses and for both MHC-I and MHC-II. Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions. Thus, our findings suggest that both cytolytic and helper T cells respond more to membrane proteins, because these are evolutionary more conserved. We speculate that TMHs therefor are less prone to escape mutations that enable pathogens to evade T cell responses.

scholarly journals Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques

2017 ◽  
Author(s):  
Matthew R. Semler ◽  
Roger W. Wiseman ◽  
Julie A. Karl ◽  
Michael E. Graham ◽  
Samantha M. Gieger ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Full Length ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Pacific Biosciences ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
The Impact

AbstractPig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to inferMane-AandMane-Bhaplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313Mane-A,Mane-B, andMane-Isequences that defined 86Mane-Aand 106Mane-BMHC-I haplotypes. Pacific Biosciences technology allows us to resolve theseMane-AandMane-Bhaplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

Interferon beta modulates major histocompatibility complex class I (MHC I) and CD3-zeta expression in PC12 cells

2012 ◽  
Vol 513 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Rodrigo Fabrizzio Inácio ◽  
Renata Graciele Zanon ◽  
Liana Verinaud ◽  
Alexandre Leite Rodrigues de Oliveira
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Pc12 Cells ◽  
Interferon Beta ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

scholarly journals A Mechanistic Basis for the Co-evolution of Chicken Tapasin and Major Histocompatibility Complex Class I (MHC I) Proteins

2013 ◽  
Vol 288 (45) ◽  
pp. 32797-32808 ◽  
Author(s):  
Andy van Hateren ◽  
Rachel Carter ◽  
Alistair Bailey ◽  
Nasia Kontouli ◽  
Anthony P. Williams ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Mechanistic Basis

scholarly journals Distinct Trafficking Pathways Mediate Nef-Induced and Clathrin-Dependent Major Histocompatibility Complex Class I Down-Regulation

2000 ◽  
Vol 74 (19) ◽  
pp. 9256-9266 ◽  
Author(s):  
Sylvie Le Gall ◽  
Florence Buseyne ◽  
Alicja Trocha ◽  
Bruce D. Walker ◽  
Jean-Michel Heard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Down Regulation ◽  
Class I Mhc ◽  
Mhc I ◽  
Heavy Chains ◽  
Histocompatibility Complex

ABSTRACT The human immunodeficiency virus type 1 Nef protein alters the post-Golgi stages of major histocompatibility complex class I (MHC-I) biogenesis. Presumed mechanisms involve the disclosure of a cryptic tyrosine-based sorting signal (YSQA) located in the cytoplasmic tail of HLA-A and -B heavy chains. We changed this signal for a prototypic sorting motif (YSQI or YSQL). Modified HLA-A2 molecules, termed A2-endo, displayed constitutively low surface levels and accumulated in a region close to or within the Golgi apparatus, a behavior reminiscent of wild-type HLA-A2 in Nef-expressing cells. However, several lines of evidence indicate that the action of prototypic signals on MHC-I trafficking differs from that of Nef. Internalization of surface A2-endo was more rapid and was associated with efficient recycling to the surface. A transdominant-negative mutant of dynamin-1 inhibited A2-endo constitutive internalization and Nef-induced CD4 down-regulation, whereas it did not affect the activity of Nef on MHC-I. Moreover, trafficking of A2-endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef. Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation.

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