Isoforms of the nonclassical class I MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide

Renthal, Nora E.; Guidry, Paula A.; Shanmuganad, Sharmila; Renthal, William; Stroynowski, Iwona

doi:10.1007/s00251-010-0488-2

Cited by 4 publications

(7 citation statements)

References 42 publications

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“…In cod, we found one transcript originating from a beard library (GenBank accession GW844691.1, Additional file 4 : Text S1) and one match from a brain transcriptome library (Additional file 4 : Text S1, SRA dataset SRX148752) while transcriptomes from the immunologically important tissues spleen, hindgut and head kidney in addition to the organs heart, gonad and liver (SRA053026) were all negative. Also tetraodon displayed P lineage expression in the brain (SRA dataset SRX191169) suggesting P genes have a biological role in teleost brain potentially in line with the roles emerging for mammalian classical as well as non-classical MHCI molecules in brain development and function [ 79 - 81 ]. Expression of classical MHCI in developing fish brain was suggested by linkage analysis to be associated with behavior such as level of boldness [ 82 , 83 ], but no studies have yet focused on the function of non-classical MHCI in fish brains.…”

Section: Resultsmentioning

confidence: 99%

A comprehensive analysis of teleost MHC class I sequences

Grimholt¹,

et al. 2015

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BackgroundMHC class I (MHCI) molecules are the key presenters of peptides generated through the intracellular pathway to CD8-positive T-cells. In fish, MHCI genes were first identified in the early 1990′s, but we still know little about their functional relevance. The expansion and presumed sub-functionalization of cod MHCI and access to many published fish genome sequences provide us with the incentive to undertake a comprehensive study of deduced teleost fish MHCI molecules.ResultsWe expand the known MHCI lineages in teleosts to five with identification of a new lineage defined as P. The two lineages U and Z, which both include presumed peptide binding classical/typical molecules besides more derived molecules, are present in all teleosts analyzed. The U lineage displays two modes of evolution, most pronouncedly observed in classical-type alpha 1 domains; cod and stickleback have expanded on one of at least eight ancient alpha 1 domain lineages as opposed to many other teleosts that preserved a number of these ancient lineages. The Z lineage comes in a typical format present in all analyzed ray-finned fish species as well as lungfish. The typical Z format displays an unprecedented conservation of almost all 37 residues predicted to make up the peptide binding groove. However, also co-existing atypical Z sub-lineage molecules, which lost the presumed peptide binding motif, are found in some fish like carps and cavefish. The remaining three lineages, L, S and P, are not predicted to bind peptides and are lost in some species.ConclusionsMuch like tetrapods, teleosts have polymorphic classical peptide binding MHCI molecules, a number of classical-similar non-classical MHCI molecules, and some members of more diverged MHCI lineages. Different from tetrapods, however, is that in some teleosts the classical MHCI polymorphism incorporates multiple ancient MHCI domain lineages. Also different from tetrapods is that teleosts have typical Z molecules, in which the residues that presumably form the peptide binding groove have been almost completely conserved for over 400 million years. The reasons for the uniquely teleost evolution modes of peptide binding MHCI molecules remain an enigma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0309-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

A comprehensive analysis of teleost MHC class I sequences

Grimholt¹,

et al. 2015

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“…In Atlantic cod, the single P lineage gene was not expressed in immunologically-important tissues such as spleen, hind gut, and head kidney underlining its nonclassical nature. However, both cod as well as tetraodon displayed P lineage expression in brain, suggesting that this gene may be involved in brain development and function similar to the emerging roles of mammalian nonclassical MHCI molecules in this organ [ 55 , 56 , 57 ].…”

Section: Teleost Mhcmentioning

confidence: 99%

MHC and Evolution in Teleosts

Grimholt

2016

Biology

123

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Major histocompatibility complex (MHC) molecules are key players in initiating immune responses towards invading pathogens. Both MHC class I and class II genes are present in teleosts, and, using phylogenetic clustering, sequences from both classes have been classified into various lineages. The polymorphic and classical MHC class I and class II gene sequences belong to the U and A lineages, respectively. The remaining class I and class II lineages contain nonclassical gene sequences that, despite their non-orthologous nature, may still hold functions similar to their mammalian nonclassical counterparts. However, the fact that several of these nonclassical lineages are only present in some teleost species is puzzling and questions their functional importance. The number of genes within each lineage greatly varies between teleost species. At least some gene expansions seem reasonable, such as the huge MHC class I expansion in Atlantic cod that most likely compensates for the lack of MHC class II and CD4. The evolutionary trigger for similar MHC class I expansions in tilapia, for example, which has a functional MHC class II, is not so apparent. Future studies will provide us with a more detailed understanding in particular of nonclassical MHC gene functions.

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“…Splice isoforms of Q5 appear to be enriched in brain (Renthal et al, 2011). Intriguingly, alternative splicing of MHCI genes was detected in hippocampus, but not at the NMJ.…”

Section: Discussionmentioning

confidence: 99%

“…The locations of primer binding determine the size of the predicted product, and also define the sequence area within which alternative splicing events will be detected. MHCI transcript skeleton adapted from (Renthal et al, 2011). …”

Section: Figurementioning

confidence: 99%

Expression and alternative splicing of classical and nonclassical MHCI genes in the hippocampus and neuromuscular junction

Tetruashvily

Melson

Park

et al. 2016

Molecular and Cellular Neuroscience

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The major histocompatibility complex class I (MHCI) is a large gene family, with over 30 members in mouse. Some MHCIs are well-known for their critical roles in the immune response. Studies in mice which lack stable cell-surface expression of many MHCI proteins suggest that one or more MHCIs also play unexpected, essential roles in the establishment, function, and modification of neuronal synapses in the central nervous system (CNS). However, there is little information about which genes mediate MHCI’s effects in neurons. In this study, RT-PCR was used to simultaneously assess transcription of many MHCI genes in regions of the central and peripheral nervous system where MHCI has a known or suspected role. In the hippocampus, a part of the CNS where MHCI regulates synapse density, synaptic transmission, and plasticity, we found that more than a dozen MHCI genes are transcribed. Single-cell RT-PCR revealed that individual hippocampal neurons can express more than one MHCI gene, and that the MHCI gene expression profile of CA1 pyramidal neurons differs significantly from that of CA3 pyramidal neurons or granule cells of the dentate gyrus. MHCI gene expression was also assessed at the neuromuscular junction (NMJ), a part of the peripheral nervous system (PNS) where MHCI plays a role in neuronal regeneration, and could potentially influence developmental synapse elimination. Four MHCI genes are expressed at the NMJ at an age when synapse elimination is occurring in three different muscles. Several MHCI mRNA splice variants were detected in hippocampus, but not at the NMJ. Together, these results establish the first profile of MHCI gene expression at the developing NMJ, and demonstrate that MHCI gene expression is under tight spatial and temporal regulation in the nervous system. They also identify more than a dozen MHCIs that could play important roles in synaptic transmission and plasticity in the central and peripheral nervous systems.

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Isoforms of the nonclassical class I MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide

Cited by 4 publications

References 42 publications

A comprehensive analysis of teleost MHC class I sequences

A comprehensive analysis of teleost MHC class I sequences

MHC and Evolution in Teleosts

Expression and alternative splicing of classical and nonclassical MHCI genes in the hippocampus and neuromuscular junction

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