| 333331. |
- Holmdahl, Meirav, et al.
(författare)
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Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.
- 2004
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377. ; 16:5, s. 717-726
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Tidskriftsartikel (refereegranskat)abstract
- Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing.
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| 333332. |
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| 333333. |
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| 333334. |
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| 333335. |
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| 333336. |
- Holmdahl, Meirav, et al.
(författare)
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Primed B cells present type-II collagen to T cells.
- 2002
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 55:4, s. 382-389
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Tidskriftsartikel (refereegranskat)abstract
- Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on a T-cell mediated activation of autoreactive B cells. However, it is still unclear if B cells can present CII to T cells. To investigate the role of B cells as antigen-presenting cells (APCs) for CII, we purified B cells from lymph nodes of immunized and nonimmunized mice. These B cells were used as APC for antigen-specific T-cell hybridomas. B cells from naïve mice did present native, triple-helical, CII (nCII) but also ovalbumin (OVA) and denatured CII (dCII) to antigen-specific T-cell hybridomas. In addition, B cells primed with nCII or OVA, but not dCII, activated the antigen-specific T-cell hybridomas two to three times better than naïve B cells. We conclude that antigen-primed B cells have the capacity to process and present CII to primed T cells, and antigen-primed antigen-specific B cells are more efficient as APC than naïve B cells. We further conclude that B cells have the potential to play an important role as APC in the development of CIA.
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| 333337. |
- Holmdahl, Meirav, et al.
(författare)
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Structure-Immune Response Relationships of Hapten-Modified Collagen II Peptides in a T-Cell Model of Allergic Contact Dermatitis.
- 2008
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 21, s. 1514-1523
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis (ACD) is mediated by T cells that specifically recognize hapten-modified peptides. T cells are known to recognize antigens as short processed peptides bound to major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APC). It has previously been demonstrated that T cells can specifically recognize carbohydrates on the lysine at position 264 of the immunodominant (256-273) sequence from type II collagen (CII) and that such recognition is critical for the development of arthritis in mice and may play a role in rheumatoid arthritis in humans. In the present study, we have used this approach in modeling ACD, but instead of the carbohydrate, the strong sensitizer 2,4-dinitrofluorobenzene (DNFB) is bound to the epsilon-amine of the lysine at position 264. Specific T-cell hybridomas of this antigenic peptide, with dinitrophenyl (Dnp) on the epsilon-amine of lysine at position 264 (CIILysDnp 3), were established from mice immunized with CIILysDnp 3. In an immune response assay, these T-cell hybridomas were tested with a series of new synthetic hapten-modified peptides, all chemically identical except for the stereochemimistry ( d, l) and the length of the position-264 amino acid side chain bonding the hapten. The T-cell hybridomas recognized the CIILysDnp 3 peptide used for immunization; interestingly, they also recognized the CII peptide with a one-carbon-longer side chain (homolysine), CIIhLysDnp 6, and CIIAlaPipDnp 11, having a ring structure analogous to that of lysine with the same number of carbons in the bonding chain as in the CIILysDnp 3 peptide used for immunization. Dnp-modified CII peptides with a shorter bonding chain produced no immune response. These data demonstrate that the T-cell recognition of the Dnp-modified peptides is highly specific and moreover dependent on the length of the amino acid side chain that bonds the Dnp.
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| 333338. |
- Holmdahl, Per, et al.
(författare)
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Continued growth after fixation of slipped capital femoral epiphysis.
- 2016
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Ingår i: Journal of children's orthopaedics. - : SAGE Publications. - 1863-2521 .- 1863-2548. ; 10:6, s. 643-650
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Tidskriftsartikel (refereegranskat)abstract
- When treating slipped capital femoral epiphysis (SCFE), a smooth pin with a hook or a short threaded screw can be used to allow further growth, which could be important to prevent the development of impingement and early arthritis. The purpose of this investigation was to measure growth in three dimensions after fixation of SCFE.Sixteen participants with unilateral SCFE, nine girls and seven boys with a median age of 12.0years (range 8.4-15.7years), were included. The slipped hip was fixed with a smooth pin with a hook, and the non-slipped hip was prophylactically pinned. At the time of surgery, tantalum markers were installed bilaterally on each side of the growth plate through the drilled hole for the pin. Examination with radiostereometric analysis (RSA) was performed postoperatively and at 3, 6 and 12months. The position of the epiphysis in relation to the metaphysis was calculated.At 12months, the epiphysis moved caudally, median 0.16mm and posteriorly 2.28mm on the slipped side, in comparison to 2.28 cranially and 0.91mm posteriorly on the non-slipped side, p=0.003 and p=0.030, respectively. Both slipped and non-slipped epiphysis moved medially, 1.52 and 1.74mm, respectively. A marked variation in the movement was noted, especially on the slipped side.The epiphysis moved in relation to the metaphysis after smooth pin fixation, both on the slipped side and on the prophylactically fixed non-slipped side, implying further growth. The RSA method can be used to understand remodelling after 'growth-sparing' fixation of SCFE.
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| 333339. |
- Holmdahl, Rikard
(författare)
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Aire-ing self antigen variability and tolerance.
- 2007
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 37:3, s. 598-601
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Tidskriftsartikel (refereegranskat)abstract
- Positional cloning of the underlying genes for the rare syndrome autoimmune polyendocrinopathy candidadiasis extrodermal dystrophy (APECED) opened a new venue of research on the role of central tolerance in autoimmunity. The associated autoimmune regulator gene (AIRE), was found to be expressed in medullary thymus epithelial cells (mTEC) in both man and mice, and to control promiscuous expression of sets of self antigens. The lack of AIRE in both mice and man led to the development of a quite specific, but also an inter-individual variable, set of autoimmune and infectious diseases. An article in this issue of the European Journal of Immunology demonstrates that several autoantigens controlled by AIRE are variably expressed in different human individuals. Most importantly it is shown that carriers of the type 1 diabetes (T1D) associated locus IDDM2 show lower expression of insulin in mTEC, as controlled by AIRE. The genetic variability of autoantigen expression in the thymus thus seems to determine the variable predisposition to autoimmunity.
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| 333340. |
- Holmdahl, R
(författare)
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At last - rats lacking B cells
- 2010
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 40:10, s. 2680-2681
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Tidskriftsartikel (refereegranskat)
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