| 1. |
- Aveskogh, Maria, et al.
(författare)
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Cloning and structural analysis of IgM (μ chain) and the heavy chain V region repertoire in the marsupial Monodelphis domestica
- 1999
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Ingår i: Developmental and Comparative Immunology. - 0145-305X .- 1879-0089. ; 23:7-8, s. 597-606
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Tidskriftsartikel (refereegranskat)abstract
- To address the question of the Ig isotype repertoire of non placental mammals, we have examined the Ig expression in the marsupial Monodelphis domestica (grey short tailed opossum). Screening of an opossum spleen cDNA library has previously led to the isolation of full length clones for opossum IgG (γ chain), IgE (ε chain) and IgA (α chain). We now present the isolation of several cDNA clones encoding the entire constant regions of the opossum IgM (μ chain). A comparative analysis of the amino acid sequences for IgM from various animal species showed that opossum IgM, within the various animals studied, is the most divergent member of its Ig class. However, it still conforms to the general structure of IgM in other vertebrates. Four Ig classes have now been identified in opossum and only one isotype is apparently present within each Ig class, IgM, IgG, IgA and IgE. Opossum has previously been shown to have a limited VH region diversity, with only two V gene families. Both of these belong to the group III of mammalian VH sequences. This limitation in variability is to some extent compensated for by a large variation in D, P and N regions, both in size and in sequence. However, evidence for the expression of only two functional J segments has so far been detected, which indicates a rather limited diversity also of the J segments in the opossum.
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| 2. |
- Gallwitz, Maike, 1977-
(författare)
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Sculpted through Time : Evolution and Function of Serine Proteases from the Mast Cell Chymase Locus
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Immune cells like NK cells, T cells, neutrophils and mast cells store high amounts of granule serine proteases, graspases. Graspases are encoded from the mast cell chymase locus. The human locus holds four genes: α-chymase, cathepsin G, and granzymes H and B. In contrast, the mouse locus contains at least 14 genes. Many of these belong to subfamilies not found in human, e.g. the Mcpt8-family. These differences hamper functional comparisons of graspases and of immune cells in the two species. Studies of the mast cell chymase locus are therefore important to better understand the mammalian immune system. In this thesis, the evolution of the mast cell chymase locus was analysed by mapping the locus in all available mammalian genome sequences. It was revealed that one single ancestral gene founded this locus probably over 215 million years ago. This ancestor was duplicated more than 185 million years ago. One copy evolved into the α-chymases, whereas the second copy founded the families of granzymes B and H, cathepsin G, Mcpt8 and duodenases. Different subfamilies were later remarkably expanded in particular mammalian lineages, e.g. the Mcpt8- and Mcpt2-subfamilies in the rat. Four novel members of these families were identified in rat mucosal mast cells. Rat and mouse mast cells express numerous different graspases, whereas human and dog mast cells express only one graspase, chymase. To better understand mast cell functions in these species, one member of the mouse Mcpt8-family, mMCP-8, and human and dog chymase were studied. The preferred substrate sequence was analysed by substrate phage display. mMCP-8 remains yet enigmatic, although it is probably proteolytically active. Dog and human chymase, interestingly, have common preferences in certain substrate positions, but differ in others. These two chymases may have coevolved with an in vivo substrate that is conserved only in the positions with a common preference. We also obtained evidence that substrate positions on either side of the scissile bond influence each other. This kind of interactions can only be detected with a method investigating both sides simultaneously, such as substrate phage display.
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| 3. |
- Wernersson, Sara, et al.
(författare)
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Granzyme-like sequences in bony fish shed light on the emergence of hematopoietic serine proteases during vertebrate evolution
- 2006
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 30:10, s. 901-918
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic serine proteases (SPs) are stored in the granules of different leukocytes and these enzymes are important effector molecules in the immune system of mammals. However, very little is known about the presence of these proteins in lower vertebrates. Herein, the primary structures of five novel fish SPs, from the Atlantic cod (Gadus morhua) and the channel catfish (Ictalurus punctatus), are presented. One of the cod SPs is a homologue to human GzmA and K. The other fish SPs identified are termed 'Gzm-like' and are distantly related to a large heterogeneous group of hematopoietic SPs, including most of the T-cell Gzms (B-H), the mast cell chymases, the mast cell/basophil proteases of the mouse mast cell protease-8 subfamily (W-family) and the neutrophil cathepsin G. Extensive BLAST-searches in genome and expressed sequence tag (EST) databases identified 40 additional teleost SPs related to the mammalian hematopoietic SP family. Subsequent phylogenetical analyses clearly demonstrate that the diversification into different subgroups within the GzmB/chymase/cathepsin G-related family has occurred independently in bony fishes and in mammals. In contrast, our findings suggest that the three subgroups, including (1) GzmK and the potent apoptosis-inducing GzmA, (2) the neutrophil proteases (proteinase 3, N-elastase and azurocidin), and (3) adipsin, have all evolved as distinct groups before the separation of tetrapods from the ray-finned fish approximately 420 million years ago.
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| 4. |
- Edholm, Eva-Stina, et al.
(författare)
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Identification of Ig sigma and Ig lambda in channel catfish, Ictalurus punctatus, and Ig lambda in Atlantic cod, Gadus morhua
- 2009
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 61:5, s. 353-370
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin light (IGL) chain genes encoding sigma and lambda from channel catfish, Ictalurus punctatus, and lambda from Atlantic cod, Gadus morhua, were identified by mining of expressed sequence tag databases, 5'-RACE and RT-PCR protocols. cDNAs for each of these IGL chains encode typical variable (V), joining (J), and constant (C) regions and Southern blot analyses and genomic sequencing show that genes encoding these isotypes, like other teleost IGL genes, are found in a cluster organization of one or two V gene segments, followed by single J and C gene segments, all in the same transcriptional orientation. However, unlike the teleost kappa genes, genes encoding catfish sigma and lambda are few in number and the two isotypes are each encoded by only two clusters. Similarly, Atlantic cod lambda genes are predicted to be encoded by two or three clusters. As expected, sequence and phylogenetic analyses comparisons demonstrate that catfish V sigma and C sigma genes are most similar to V sigma and C sigma genes of other ectothermic vertebrates. Although catfish and Atlantic cod V lambda genes cluster with other vertebrate V lambda genes, their C lambda sequences cluster in a distinct group separate from other vertebrate IGL C sequences. However, support for classifying these sequences as lambda, is their V and J recombination signal sequence (RSS) organization. The catfish and Atlantic cod genes have typical lambda-like RSS with the V lambda RSS consisting of heptamer-23 bp spacer-nonamer and the J lambda RSS consisting of heptamer-12 bp spacer-nonamer. This is the first report demonstrating the presence of Ig lambda in teleosts.
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| 5. |
- Lundqvist, Mats, et al.
(författare)
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Diverse splicing pathways of the membrane IgHM pre-mRNA in a Chondrostean, the Siberian sturgeon
- 2009
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 33:4, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- Teleosts and tetrapods have evolved different splice patterns to generate their membrane-bound IgM. In the tetrapod lineage, the first transmembrane exon is spliced to an internal cryptic site located close to the end of the fourth constant exon. Because teleosts lack this site they use the regular T-splice site of the CH3 exon instead. We characterized the mu m splicing patterns in a Chondrostean, the Siberian sturgeon. We observed a surprising diversity of splice patterns, the TM1 exon being spliced to a cryptic site at the end of CH4, to a cryptic site in CH3 or to the 3'-end of CHI. These different pathways lead to m1GHM transcripts encoding four, two or one complete C-domain(s), respectively. The short variant CH1-TM1 was found only in VH2 positive transcripts, while the two other variants were observed for IgHM transcripts expressing all VH families. These results shed light on the evolution of IgM splicing pathways.
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| 6. |
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