scholarly journals Major histocompatibility complex selection dynamics in pathogen-infected túngara frog ( Physalaemus pustulosus ) populations

2016 ◽  
Vol 12 (8) ◽  
pp. 20160345 ◽  
Author(s):  
Tiffany A. Kosch ◽  
Arnaud Bataille ◽  
Chelsea Didinger ◽  
John A. Eimes ◽  
Sofia Rodríguez-Brenes ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Balancing Selection ◽  
Directional Selection ◽  
Major Histocompatibility ◽  
Physalaemus Pustulosus ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Selection Dynamics

Pathogen-driven selection can favour major histocompatibility complex (MHC) alleles that confer immunological resistance to specific diseases. However, strong directional selection should deplete genetic variation necessary for robust immune function in the absence of balancing selection or challenges presented by other pathogens. We examined selection dynamics at one MHC class II (MHC-II) locus across Panamanian populations of the túngara frog, Physalaemus pustulosus , infected by the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). We compared MHC-II diversity in highland túngara frog populations, where amphibian communities have experienced declines owing to Bd, with those in the lowland region that have shown no evidence of decline. Highland region frogs had MHC variants that confer resistance to Bd. Variant fixation appeared to occur by directional selection rather than inbreeding, as overall genetic variation persisted in populations. In Bd-infected lowland sites, however, selective advantage may accrue to individuals with only one Bd-resistance allele, which were more frequent. Environmental conditions in lowlands should be less favourable for Bd infection, which may reduce selection for specific Bd resistance in hosts. Our results suggest that MHC selection dynamics fluctuate in túngara frog populations as a function of the favourability of habitat to pathogen spread and the vulnerability of hosts to infection.

scholarly journals MPYS, a Novel Membrane Tetraspanner, Is Associated with Major Histocompatibility Complex Class II and Mediates Transduction of Apoptotic Signals

2008 ◽  
Vol 28 (16) ◽  
pp. 5014-5026 ◽  
Author(s):  
Lei Jin ◽  
Paul M. Waterman ◽  
Karen R. Jonscher ◽  
Cindy M. Short ◽  
Nichole A. Reisdorph ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Death Signals

ABSTRACT Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (∼140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.

scholarly journals Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole ( Arvicola terrestris )

2008 ◽  
Vol 276 (1659) ◽  
pp. 1119-1128 ◽  
Author(s):  
M.K Oliver ◽  
S Telfer ◽  
S.B Piertney
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Balancing Selection ◽  
Parasite Burden ◽  
Island Population ◽  
Water Vole ◽  
Immune Recognition ◽  
Major Histocompatibility ◽  
Arvicola Terrestris ◽  
Histocompatibility Complex

The fundamental role of the major histocompatibility complex (MHC) in immune recognition has led to a general consensus that the characteristically high levels of functional polymorphism at MHC genes is maintained by balancing selection operating through host–parasite coevolution. However, the actual mechanism by which selection operates is unclear. Two hypotheses have been proposed: overdominance (or heterozygote superiority) and negative frequency-dependent selection. Evidence for these hypotheses was evaluated by examining MHC–parasite relationships in an island population of water voles ( Arvicola terrestris ). Generalized linear mixed models were used to examine whether individual variation at an MHC class II DRB locus explained variation in the individual burdens of five different parasites. MHC genotype explained a significant amount of variation in the burden of gamasid mites, fleas ( Megabothris walkeri ) and nymphs of sheep ticks ( Ixodes ricinus ). Additionally, MHC heterozygotes were simultaneously co-infected by fewer parasite types than homozygotes. In each case where an MHC-dependent effect on parasite burden was resolved, the heterozygote genotype was associated with fewer parasites, and the heterozygote outperformed each homozygote in two of three cases, suggesting an overall superiority against parasitism for MHC heterozygote genotypes. This is the first demonstration of MHC heterozygote superiority against multiple parasites in a natural population, a mechanism that could help maintain high levels of functional MHC genetic diversity in natural populations.

scholarly journals Processing of Mycobacterium tuberculosis Antigen 85B Involves Intraphagosomal Formation of Peptide–Major Histocompatibility Complex II Complexes and Is Inhibited by Live Bacilli that Decrease Phagosome Maturation

2001 ◽  
Vol 194 (10) ◽  
pp. 1421-1432 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Erika Noss ◽  
W. Henry Boom ◽  
Clifford V. Harding
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Immune Surveillance ◽  
Interferon Γ ◽  
Hybridoma Cells ◽  
Phagosome Maturation ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex

Mycobacterium tuberculosis (MTB) inhibits phagosomal maturation to promote its survival inside macrophages. Control of MTB infection requires CD4 T cell responses and major histocompatibility complex (MHC) class II (MHC-II) processing of MTB antigens (Ags). To investigate phagosomal processing of MTB Ags, phagosomes containing heat-killed (HK) or live MTB were purified from interferon-γ (IFN-γ)–activated macrophages by differential centrifugation and Percoll density gradient subcellular fractionation. Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM. T hybridoma cells were used to detect MTB Ag 85B(241–256)–I-Ab complexes in isolated phagosomes and other subcellular fractions. These complexes appeared initially (within 20 min) in phagosomes and subsequently (>20 min) on the plasma membrane, but never within late endocytic compartments. Macrophages processed HK MTB more rapidly and efficiently than live MTB; phagosomes containing live MTB expressed fewer Ag 85B(241–256)–I-Ab complexes than phagosomes containing HK MTB. This is the first study of bacterial Ag processing to directly show that peptide–MHC-II complexes are formed within phagosomes and not after export of bacterial Ags from phagosomes to endocytic Ag processing compartments. Live MTB can alter phagosome maturation and decrease MHC-II Ag processing, providing a mechanism for MTB to evade immune surveillance and enhance its survival within the host.

scholarly journals Presentation of Exogenous Antigens on Major Histocompatibility Complex (MHC) Class I and MHC Class II Molecules Is Differentially Regulated during Dendritic Cell Maturation

2003 ◽  
Vol 198 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Lélia Delamarre ◽  
Hilda Holcombe ◽  
Ira Mellman
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Dendritic Cell Maturation ◽  
Mouse Bone Marrow ◽  
Major Histocompatibility ◽  
Cd40 Ligation ◽  
Mhc I ◽  
Cross Presentation ◽  
Mhc Ii ◽  
Histocompatibility Complex

During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II–restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow–derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide–MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell–cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide–MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

Cellular and Gene Therapy for Major Histocompatibility Complex Class II Deficiency

Physiology ◽  
2004 ◽  
Vol 19 (3) ◽  
pp. 154-158 ◽  
Author(s):  
Franck Matheux ◽  
Jean Villard
Keyword(s):  
Gene Therapy ◽  
Major Histocompatibility Complex ◽  
Mouse Model ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Deficiency

Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized.

scholarly journals CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

2010 ◽  
Vol 30 (17) ◽  
pp. 4211-4223 ◽  
Author(s):  
Parimal Majumder ◽  
Jeremy M. Boss
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Mhc Class Ii ◽  
Gene Promoter ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Human Major Histocompatibility Complex ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divide the MHC-II locus into apparent evolutionary domains were identified. To define the role of CTCF in mediating regulation of the MHC II genes, chromatin conformation capture assays, which provide an architectural assessment of a locus, were conducted across the MHC-II region. Depending on whether MHC-II genes and the class II transactivator (CIITA) were being expressed, two CTCF-dependent chromatin architectural states, each with multiple configurations and interactions, were observed. These states included the ability to express MHC-II gene promoter regions to interact with nearby CTCF sites and CTCF sites to interact with each other. Thus, CTCF organizes the MHC-II locus into a novel basal architecture of interacting foci and loop structures that rearranges in the presence of CIITA. Disruption of the rearranged states eradicated expression, suggesting that the formation of these structures is key to coregulation of MHC-II genes and the locus.

Sign in / Sign up

Export Citation Format

Share Document