| 1. |
- Dzhambazov, Balik, et al.
(författare)
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The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans
- 2005
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 35:2, s. 357-366
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.
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| 2. |
- Dzhambazov, Balik, et al.
(författare)
-
The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans
- 2005
-
Ingår i: EUROPEAN JOURNAL OF IMMUNOLOGY. - : Wiley. - 0014-2980 .- 1521-4141. ; 35:2, s. 357-66
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.
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| 3. |
- Teneva, I, et al.
(författare)
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Cytotoxicity and apoptotic effects of microcystin-LR and anatoxin-a in mouse lymphocytes
- 2005
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Ingår i: Folia Biologica. - 0015-5500. ; 51:3, s. 62-67
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Tidskriftsartikel (refereegranskat)abstract
- There is an increasing amount of knowledge on the cytotoxic properties of cyanotoxins, but relatively little is known regarding their fine specificity and mechanisms of action. In this study, we investigated the influence of microcystin-LR and AnTx-a on mouse B- and T-lymphocyte subpopulations in vitro. Cyanotoxins significantly decreased the cell viability after 4 and 24 h, compared to the untreated control. After 24 h exposure to microcystin-LR and anatoxin-a, the viability of splenocytes dropped to 23% and 57%, respectively. Our data demonstrate that microcystin-LR induced apoptosis specifically in mouse B cells, probably via the B-cell antigen receptor and mitochondrial pathway, while the T cells were not affected. AnTx-a showed cytotoxic effects on both lymphocyte subpopulations, but the effects were driven by mechanisms different from apoptosis. These findings demonstrate that the cyanotoxins could cause cytotoxic alterations in a variety of cell types different from the major targets, operating via distinct mechanisms.
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| 4. |
- Teneva, Ivanka, et al.
(författare)
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Molecular and phylogenetic characterization of Phormidium species (Cyanoprokaryota) using the cpcB-IGS-cpcA locus
- 2005
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Ingår i: Journal of Phycology. - : Wiley. - 0022-3646 .- 1529-8817. ; 41:1, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- The accurate determination of species of Cyanoprokaryota/Cyanophyceae has many important applications. These include the assessment of risk with regard to blooms in water reservoirs as well as the identification of species capable of producing valuable bioactive compounds. Commonly, Cyanoprokaryota are classified based on their morphology. However, morphological criteria are not always reliable because they may change, for example, due to environmental factors. Thus, genetic and molecular analyses are a promising additional approach, but their application has so far been limited to relatively few genera. In light of this, we present here the first characterization of species and strains of the genus Phormidium Kutz. based on the cpcB-IGS-cpcA locus of the phycocyanin operon. In phylogenetic analyses using deduced amino acid sequences of the cpcB-cpcA regions, Phormidium was found to be polyphyletic. This analysis appeared to be dominated by the cpcB region, which is characterized by a relatively high percentage of informative substitutions. The percentage of variable positions within the cpcB-IGS-cpcA locus overall was 16.5%, thereby indicating a level of divergence remarkably higher than that reported for Nodularia and Arthrospira in previous studies relying on cpcB-IGS-cpcA. Further, alignment of informative nucleotide substitutions in the cpcB-IGS-cpcA sequences revealed a mosaic distribution, which may be indicative of genetic recombination events. Finally, the length and sequences of the IGS region alone proved useful as markers to differentiate the cyanobacterial genus Phormidium. However, whether the IGS region per se is sufficiently discriminatory to differentiate between Phormidium species or even strains requires further investigation using newly identified Phormidium sequence data.
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| 5. |
- Teneva, I, et al.
(författare)
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Toxic potential of five freshwater Phormidium species (Cyanoprokaryota)
- 2005
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 45:6, s. 711-725
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Tidskriftsartikel (refereegranskat)abstract
- Among the Cyanoprokaryota (blue-green algae), the genus Phormidium has thus far rarely been studied with respect to toxin production and potentially resulting human and environmental health effects. We here show that five previously unexplored freshwater species of this genus (Ph. bijugatum, Ph. molle, Ph. papyraceum, Ph. uncinatum, Ph. autumnale) are indeed capable of producing bioactive compounds. Phormidium extracts caused weight loss as well as neuro/hepatotoxic symptoms in mice, and in the case of Ph. bijugatum even death. Very low levels of saxitoxins and microcystins, as confirmed by ELISA, were insufficient to explain this toxicity and the differing toxic potencies of the Phormidium species. Qualitative HPLC analyses confirmed different substance patterns and in the future could aid in the separation of fractions for more detailed substance characterisation. The results in vivo were confirmed in vitro using cells of human, mouse and fish. The fish cells responded least sensitive but proved useful in studying the temperature dependence of the toxicity by the Phormidium samples. Further, the human cells were more sensitive than the mouse cells thus suggesting that the former may be a more appropriate choice for studying the impact of Phormidium to man. Among the human cells, two cancer cell lines were more responsive to one of the samples than a normal cell line, thereby indicating a potential anti-tumour activity. Thus, the five freshwater Phormidium species should be considered in environmental risk assessment but as well, as a source of therapeutic agents.
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