Search results for "Antigens"
showing 10 items of 1928 documents
HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides
2003
SUMMARY Ankylosing spondylitis (AS) is an inflammatory systemic disease affecting the spine, sacroiliacal and peripheral joints. Although the aetiology of AS remains unknown, the strong association with the HLA-B27 allele might reflect directly a detrimental effect of the HLA-B27 molecule itself, resulting from its potential capability to present ‘arthritogenic’ peptides to CD8+ T cells. Because some forms of SpA are triggered by enterobacterial infection, such arthritogenic peptides might originate from autologous and/or bacterial proteins triggering cross-reactive CD8+ T cell clones. Intriguingly, two peptides from the second extracellular domain of HLA-B*2705 share sequence homologies wi…
HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis.
1993
Ankylosing spondylitis and seronegative spondylarthropathies such as Reiter's syndrome and reactive arthritis are strongly associated with HLA-B27. However, the mechanisms by which HLA-B27 is involved in disease susceptibility and pathogenesis are unknown. If the disease association is a consequence of HLA-B27's physiological function in antigen presentation, the disease should be mediated by cytotoxic T lymphocytes (CTLs) that recognise bacterial or self peptides presented by HLA-B27. Proof of this arthritogenic peptide model requires isolation of B27-restricted CD8 T cells from arthritic joints of patients with spondylarthropathies. An important question is whether "arthritogenic" bacteri…
HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segm…
1996
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes wit…
HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity.
2015
The HLA class II genes are susceptibility genes for autoimmune endocrine diseases; however, scarce data are available pertaining to the determinants of genetic susceptibility to polyglandular autoimmunity (PGA). A total of 300 consecutive and unselected patients with either PGA or monoglandular autoimmune thyroid disease (AITD) and 100 healthy control subjects were genotyped for the HLA class II DRB1, -DQA1, and -DQB1 alleles. Compared to patients with AITD and controls, the HLA-DRB1*03 (pc =0.001), *04 (pc<0.001), -DQA1*03 (pc<0.001), and -DQB1*02 (pc =0.001) alleles were increased in patients with PGA. When dividing patients with Hashimoto's thyroiditis (HT) into those with PGA (PGA-HT) v…
Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians
2008
Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a ro…
Bacteria-specific cytotoxic CD8+ T cells: a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies.
1994
The term seronegative spondylarthropathies is used for an entity of rheumatic syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel disease) which are strongly associated with the MHC class I molecule HLA-B27. However, the mechanisms whereby HLA-B27 confers disease susceptibility have so far remained unknown. There is strong evidence that gut inflammation and infection with gram-negative bacteria play a role in the induction of B27-associated disease. HLA-B27, like other MHC class I molecules, physiologically binds antigenic peptides in its binding groove and presents them to CD8+ T lymph…
Enterobacterial Antigens with Tropism for Joint Structures and HLA-B27=Restricted Cytotoxic T-Cells in Reactive Arthritis
1995
In reactive arthritis (ReA), sterile synovitis is an immunological sequela following gastrointestinal or urogenital infection with facultatively intracellular bacteria (Yersinia, Salmonella, Shigella, Chlamydia). It is widely accepted now that the development of arthritis is closely related to the persistance of bacteria or bacterial antigens in extraarticular mucosal or lymphoid tissues (i.e. gut mucosa, gut associated lymphoid tissue, genitourinary mucosa); however, it is still unclear which host mechanisms are responsible for the poorer elimination of arthritis-causing microorganisms in those ReA patients. Bacterial components are also camed to the joints where they can be demonstrated i…
H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove.
1996
The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibilityI-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequencedH2-Ma, H2-Mb1, andH2-Mb2 genes from CIA-susceptible and-resistant mouse strains and identified four differentMa andMb2 alleles and three differentMb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share commonMa, M…
Identification of the Yersinia enterocolitica urease beta subunit as a target antigen for human synovial T lymphocytes in reactive arthritis.
1993
The local T-cell response to bacterial antigens is involved in the pathogenesis of reactive arthritis (ReA). Here, we have identified a 19-kDa antigen of Yersinia enterocolitica O:9 recognized by Yersinia-specific synovial fluid CD4+ T cells in two patients with Yersinia-induced ReA. N-terminal amino acid sequencing of this protein revealed that it was identical to the 19-kDa urease beta subunit of Y. enterocolitica O:9. This protein has previously been shown to be arthritogenic in preimmunized rats after intra-articular injection. Analysis of the T-cell response to this protein showed that it contains several T-cell epitopes, one of which cross-reacts with other enterobacteria not able to …
Sequence analysis of the DRB1 promoter reveals limited polymorphism with no influence on gene expression.
2001
HLA-class II promoters contain a set of conserved regulatory regions necessary for constitutive and induced gene expression. For the HLA-DQB as well as for the DRB1 promoter sequence, polymorphisms with influence on gene expression have been reported. In contrast to these data we could show that there is very limited allele-specific polymorphism among the HLA-DRB1 promoter alleles. In a long range PCR we amplified a DNA sequence containing the promoter and the second exon of the DRB1 gene in one fragment. Nested PCR products of this PCR fragment for the promoter and for the second exon were analysed by DNA sequencing to allow the linkage of a promoter to its DR allele. Most investigated DRB…