scholarly journals Non-random association of MHC-I alleles in favor of high diversity haplotypes in wild songbirds revealed by computer-assisted MHC haplotype inference using the R package MHCtools

2020 ◽  
Author(s):  
Jacob Roved ◽  
Bengt Hansson ◽  
Martin Stervander ◽  
Dennis Hasselquist ◽  
Helena Westerdahl

AbstractMajor histocompatibility complex (MHC) genes play a central role for pathogen recognition by the adaptive immune system. The MHC genes are often duplicated and tightly linked within a small genomic region. This structural organization suggests that natural selection acts on the combined property of multiple MHC gene copies in segregating haplotypes, rather than on single MHC genes. This may have important implications for analyses of patterns of selection on MHC genes. Here, we present a computer-assisted protocol to infer segregating MHC haplotypes from family data, based on functions in the R package MHCtools. We employed this method to identify 107 unique MHC class I (MHC-I) haplotypes in 116 families of wild great reed warblers (Acrocephalus arundinaceus). In our data, the MHC-I genes were tightly linked in haplotypes and inherited as single units, with only two observed recombination events among 334 offspring. We found substantial variation in the number of different MHC-I alleles per haplotype, and the divergence between alleles in MHC-I haplotypes was significantly higher than between randomly assigned alleles in simulated haplotypes. This suggests that selection has favored non-random associations of divergent MHC-I alleles in haplotypes to increase the range of pathogens that can be recognized by the adaptive immune system. Further studies of selection on MHC haplotypes in natural populations is an interesting avenue for future research. Moreover, inference and analysis of MHC haplotypes offers important insights into the structural organization of MHC genes, and may improve the accuracy of the MHC region in de novo genome assemblies.

2010 ◽  
Vol 16 (3) ◽  
pp. 131-137 ◽  
Author(s):  
Nades Palaniyar

Soluble pattern-recognition innate immune proteins functionally resemble the antibodies of the adaptive immune system. Two major families of such proteins are ficolins and collectins or collagenous lectins (e.g. mannose-binding lectin [MBL], surfactant proteins [SP-A and SP-D] and conglutinin). In general, subunits of ficolins and collectins recognize the carbohydrate arrays of their targets via globular trimeric carbohydrate-recognition domains (CRDs) whereas IgG, IgM and other antibody isotypes recognize proteins via dimeric antigen-binding domains (Fab). Considering the structure and functions of these proteins, ficolins and MBL are analogous to molecules with the complement activating functions of C1q and the target recognition ability of IgG. Although the structure of SP-A is similar to MBL, it does not activate the complement system. Surfactant protein-D and conglutinin could be considered as the collagenous non-complement activating giant IgMs of the innate immune system. Proteins such as peptidoglycan-recognition proteins, pentraxins and agglutinin gp-340/DMBT1 are also pattern-recognition proteins. These proteins may be considered as different isotypes of antibody-like molecules. Proteins such as defensins, cathelicidins and lactoferrins directly or indirectly alter microbes or microbial growth. These proteins may not be considered as antibodies of the innate immune system. Hence, ficolins and collectins could be considered as specialized ‘antibodies of the innate immune system’ instead of ‘ante-antibody’ innate immune molecules. The discovery, structure, functions and future research directions of many of these soluble proteins and receptors such as Toll-like and NOD-like receptors are discussed in this special issue of Innate Immunity.


2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.


mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Alexander P. Hynes ◽  
Simon J. Labrie ◽  
Sylvain Moineau

ABSTRACT The adaptive immune system of prokaryotes, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes), results in specific cleavage of invading nucleic acid sequences recognized by the cell’s “memory” of past encounters. Here, we exploited the properties of native CRISPR-Cas systems to program the natural “memorization” process, efficiently generating immunity not only to a bacteriophage or plasmid but to any specifically chosen DNA sequence. IMPORTANCE CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immunization process, we offer a means to generate customized immunity, as well as provide a new tool to study adaptation.


2012 ◽  
Vol 10 (1) ◽  
pp. 201 ◽  
Author(s):  
Gezina TML Oei ◽  
Kirsten F Smit ◽  
Djai vd Vondervoort ◽  
Daniel Brevoord ◽  
Arjan Hoogendijk ◽  
...  

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