Species divergence, selection and polymorphism in the MHC of crows

A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of positively selected amino acids by supertyping revealed a single supertype shared by only jungle and carrion crows, a pattern consistent with convergence, the overall phylogenetic patterns we observed suggest that TSP, rather than convergence, explains the interspecific allelic similarity of MHC IIB genes in these species of crows.

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Patterns of evolution of MHC Class II genes of crows (Corvus) suggest trans-species polymorphism

10.7287/peerj.preprints.621v2 ◽

2015 ◽

Author(s):

John A Eimes ◽

Andrea K Townsend ◽

Irem Sepil ◽

Isao Nishiumi ◽

Yoko Satta

Keyword(s):

Mhc Class Ii ◽

Convergent Evolution ◽

Phylogenetic Trees ◽

Balancing Selection ◽

Bird Species ◽

Evolutionary Divergence ◽

Exon 2 ◽

Synonymous Substitutions ◽

American Crows ◽

Mhc Iib

A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of positively selected amino acids by supertyping revealed a single supertype shared by only jungle and carrion crows, a pattern consistent with convergence, the overall phylogenetic patterns we observed suggest that TSP, rather than convergence, explains the interspecific allelic similarity of MHC IIB genes in these species of crows.

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Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

Pathogens ◽

10.3390/pathogens7020053 ◽

2018 ◽

Vol 7 (2) ◽

pp. 53 ◽

Cited By ~ 34

Author(s):

Stephen Tuffs ◽

S. Haeryfar ◽

John McCormick

Keyword(s):

Mhc Class Ii ◽

Class Ii ◽

Toxic Shock ◽

Cross Link ◽

Effective Response ◽

Innate And Adaptive Immunity ◽

Histocompatibility Complex ◽

High Level ◽

Evolutionary Fitness ◽

Mhc Class Ii Molecules

Staphylococcal superantigens (SAgs) constitute a family of potent exotoxins secreted by Staphylococcus aureus and other select staphylococcal species. SAgs function to cross-link major histocompatibility complex (MHC) class II molecules with T cell receptors (TCRs) to stimulate the uncontrolled activation of T lymphocytes, potentially leading to severe human illnesses such as toxic shock syndrome. The ubiquity of SAgs in clinical S. aureus isolates suggests that they likely make an important contribution to the evolutionary fitness of S. aureus. Although the apparent redundancy of SAgs in S. aureus has not been explained, the high level of sequence diversity within this toxin family may allow for SAgs to recognize an assorted range of TCR and MHC class II molecules, as well as aid in the avoidance of humoral immunity. Herein, we outline the major diseases associated with the staphylococcal SAgs and how a dysregulated immune system may contribute to pathology. We then highlight recent research that considers the importance of SAgs in the pathogenesis of S. aureus infections, demonstrating that SAgs are more than simply an immunological diversion. We suggest that SAgs can act as targeted modulators that drive the immune response away from an effective response, and thus aid in S. aureus persistence.

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MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

Journal of Personalized Medicine ◽

10.3390/jpm11060564 ◽

2021 ◽

Vol 11 (6) ◽

pp. 564

Author(s):

Chin-Man Wang ◽

Keng-Poo Tan ◽

Yeong-Jian Jan Wu ◽

Jing-Chi Lin ◽

Jian-Wen Zheng ◽

...

Keyword(s):

Immune Responses ◽

Significant Risk ◽

Significant Risk Factor ◽

Healthy Controls ◽

Hla B27 ◽

Host Immune Responses ◽

Histocompatibility Complex ◽

High Level ◽

Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

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Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy

Blood ◽

10.1182/blood-2004-10-3880 ◽

2005 ◽

Vol 105 (10) ◽

pp. 3824-3832 ◽

Cited By ~ 103

Author(s):

Peng H. Tan ◽

Sven C. Beutelspacher ◽

Shao-An Xue ◽

Yao-He Wang ◽

Peter Mitchell ◽

...

Keyword(s):

Dendritic Cell ◽

Mhc Class Ii ◽

Viral Vectors ◽

Cell Function ◽

Leukemia Virus ◽

Moloney Murine Leukemia Virus ◽

Histocompatibility Complex ◽

Immunodeficiency Virus ◽

Anemia Virus ◽

And Function

AbstractGenetic modification of dendritic-cell (DC) function is an attractive approach to treat disease, either using mature DCs (mDCs) to immunize patients, or immature DCs (iDCs) to induce tolerance. Viral vectors are efficient at transducing DCs, and we have investigated the effect of transduction with a variety of viral vectors on the phenotype and function of DCs. Adenovirus (Ad), human immunodeficiency virus (HIV), equine anemia virus (EIAV), and Moloney murine leukemia virus (MMLV) all up-regulate costimulatory molecules and major histocompatibility complex (MHC) class II expression on DCs, as well as, in the case of Ad and lentiviral vectors, inducing production of Th1 and proinflammatory cytokines. Following transduction there is activation of double-stranded (ds) RNA-triggered pathways resulting in interferon (IFN) α/β production. In addition, the function of virally infected DCs is altered; iDCs have an increased, and mDCs a decreased, ability to stimulate a mixed lymphocyte reaction (MLR). Viral transduction of mDCs results in up-regulation of the indoleamine 2,3-dioxygenase (IDO) enzyme, which down-regulates T-cell responsiveness. Inhibition of IDO restores the ability of mDCs to stimulate an MLR, indicating that IDO is responsible for the modulation of mDC function. These data have important implications for the use of viral vectors in the transduction of DCs.

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Relationship between invariant chain expression and major histocompatibility complex class II transport into early and late endocytic compartments.

Journal of Experimental Medicine ◽

10.1084/jem.177.3.583 ◽

1993 ◽

Vol 177 (3) ◽

pp. 583-596 ◽

Cited By ~ 95

Author(s):

P Romagnoli ◽

C Layet ◽

J Yewdell ◽

O Bakke ◽

R N Germain

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Class Ii ◽

Endocytic Pathway ◽

Invariant Chain ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Late Endosomes ◽

Early Endosomes ◽

Endocytic Compartments

Invariant chain (Ii), which associates with major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, contains a targeting signal for transport to intracellular vesicles in the endocytic pathway. The characteristics of the target vesicles and the relationship between Ii structure and class II localization in distinct endosomal subcompartments have not been well defined. We demonstrate here that in transiently transfected COS cells expressing high levels of the p31 or p41 forms of Ii, uncleaved Ii is transported to and accumulates in transferrin-accessible (early) endosomes. Coexpressed MHC class II is also found in this same compartment. These early endosomes show altered morphology and a slower rate of content movement to later parts of the endocytic pathway. At more moderate levels of Ii expression, or after removal of a highly conserved region in the cytoplasmic tail of Ii, coexpressed class II molecules are found primarily in vesicles with the characteristics of late endosomes/prelysosomes. The Ii chains in these late endocytic vesicles have undergone proteolytic cleavage in the lumenal region postulated to control MHC class II peptide binding. These data indicate that the association of class II with Ii results in initial movement to early endosomes. At high levels of Ii expression, egress to later endocytic compartments is delayed and class II-Ii complexes accumulate together with endocytosed material. At lower levels of Ii expression, class II-Ii complexes are found primarily in late endosomes/prelysosomes. These data provide evidence that the route of class II transport to the site of antigen processing and loading involves movement through early endosomes to late endosomes/prelysosomes. Our results also reveal an unexpected ability of intact Ii to modify the structure and function of the early endosomal compartment, which may play a role in regulating this processing pathway.

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CD1 and Major Histocompatibility Complex II Molecules Follow a Different Course during Dendritic Cell Maturation

Molecular Biology of the Cell ◽

10.1091/mbc.e02-11-0744 ◽

2003 ◽

Vol 14 (8) ◽

pp. 3378-3388 ◽

Cited By ~ 36

Author(s):

Nicole N. van der Wel ◽

Masahiko Sugita ◽

Donna M. Fluitsma ◽

Xaiochun Cao ◽

Gerty Schreibelt ◽

...

Keyword(s):

Dendritic Cells ◽

Major Histocompatibility Complex ◽

Dendritic Cell ◽

Mhc Class Ii ◽

Class Ii ◽

Dendritic Cell Maturation ◽

Cell Maturation ◽

Major Histocompatibility ◽

Mhc Molecules ◽

Histocompatibility Complex

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Herein, we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady-state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to lipopolysaccharide-induced maturation. However, the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus, the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separate peptide- and lipid antigen-presenting molecules during dendritic cell maturation.

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Hierarchy of Susceptibility of Dendritic Cell Subsets to Infection by Leishmania major: Inverse Relationship to Interleukin-12 Production

Infection and Immunity ◽

10.1128/iai.70.7.3874-3880.2002 ◽

2002 ◽

Vol 70 (7) ◽

pp. 3874-3880 ◽

Cited By ~ 31

Author(s):

Sandrine Henri ◽

Joan Curtis ◽

Hubertus Hochrein ◽

David Vremec ◽

Ken Shortman ◽

...

Keyword(s):

Immune Responses ◽

Mhc Class Ii ◽

Leishmania Major ◽

Parasitophorous Vacuole ◽

Class Ii ◽

Host Cells ◽

Interleukin 12 ◽

Histocompatibility Complex ◽

T Cell Immune Responses ◽

Antigen Presenting

ABSTRACT Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4+ CD8− DCs are the most permissive host cells for L. major amastigotes, followed by CD4− CD8− DCs; CD4− CD8+ cells are the least permissive. However, the least susceptible CD4− CD8+ DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein 1 molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.

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