| 1. |
- Popovic, M., et al.
(författare)
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Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains
- 2008
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 68:4, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- Collagen-induced arthritis (CIA) is a well studied mouse model of the human disease rheumatoid arthritis (RA). Both CIA and RA are complex diseases affected by multiple genes as well as environmental factors. Identifying the genes that determine susceptibility to arthritis would give invaluable clues to the largely unknown aetiology of RA. In this study, we dissected a known locus, Cia6, as well as a genomic region on chromosome 14 with no previously known arthritis loci, using a partial advanced intercross and a collection of congenic strains. The chromosome 14 congenic fragment, containing the T-cell receptor alpha (Tcra) locus, was included based on the hypothesis that the Cia6 locus is caused by a polymorphism in the Tcr beta (Tcrb) locus and that the two loci interact. Splitting up the congenic fragments revealed multiple loci affecting arthritis traits as well as production of collagen-specific autoantibodies. In total seven new loci were identified of which four were in the previously unlinked chromosome 14 region. Both Tcr loci were within CIA loci making them candidate susceptibility genes. The results demonstrate the importance of breaking up genetic regions in smaller fragments to identify the underlying complex set of loci.
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| 2. |
- Wester, L, et al.
(författare)
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Receptor for alpha1-microglobulin on T lymphocytes : inhibition of antigen-induced interleukin-2 production
- 1998
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 48:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- The human plasma protein alpha1-microglobulin (alpha1m) was found to inhibit the antigen-induced interleukin-2 (IL-2) production of two different mouse T-helper cell hybridomas. Alpha1m isolated from human plasma and recombinant alpha1m isolated from baculovirus-infected insect cell cultures had similar inhibitory effects. Flow cytometric analysis showed a binding of plasma and recombinant alpha1m to the T-cell hybridomas as well as to a human T-cell line. Radiolabelled plasma and recombinant alpha1m bound to the T-cell hybridomas in a saturable manner and the binding could be eliminated by trypsination of the cells. The affinity constants for the cell binding were calculated to be 0.4-1 x 10(5) M(-1) using Scatchard plotting, and the number of binding sites per cell was estimated to be 5 x 10(5)-1 x 10(6). The cell-surface proteins of one of the T-cell hybridomas were radiolabelled, the cells lysed and alpha1m-binding proteins isolated by affinity chromatography. SDS-PAGE and autoradiography analysis of the eluate revealed major bands with Mr-values around 70, 35 and 15 kDa. The results thus suggest that alpha1m binds to a specific receptor on T cells and that the binding leads to inhibition of antigen-stimulated IL-2 production by T-helper cells.
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