Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Ramos, Manuel; Álvarez, Iñaki; Sesma, Laura; Logean, Antoine; Rognan, Didier; Castro, José A. Łópez de

doi:10.1074/jbc.m205470200

Cited by 82 publications

(51 citation statements)

References 69 publications

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“…156 Abnormal forms of HLA-B27 may then present microbial or self-peptides to CD4 + T cells possibly involved in class I immune recognition and NK cells rather than CD8 + T cells. 157,158 Peptides from HLA-B27 have sequence homology with peptides from enterobacteria 159 and Chlamydia 160 with the latter also documented to possibly reactivate autoreactive cytotoxic T cells with specificity for HLA-B27. TNF-α, 161 TGF-β 162 and IL-1 163 polymorphisms have also been confirmed as possible candidate genes for susceptibility to ankylosing spondylitis.…”

Section: Ankylosing Spondylitismentioning

confidence: 99%

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Ooi¹,

Galatowicz²,

Calder³

et al. 2006

Clinical Medicine & Research

133

118

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Section: Ankylosing Spondylitismentioning

confidence: 99%

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Ooi¹,

Galatowicz²,

Calder³

et al. 2006

Clinical Medicine & Research

133

118

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“…The "arthritogenic peptide" theory focuses on the canonical functions of HLA-B27 in antigen presentation to cytotoxic T-lymphocytes. [52][53][54][55][56] The hypothesis suggests that after pathogenic insult, HLA-B27 presents a microbial epitope and elicits a CTL response against it. However, some of the CTLs may cross-react with any self antigens showing molecular mimicry with the microbial epitope.…”

Section: Hla-b27mentioning

confidence: 99%

The genomics and genetics of ankylosing spondylitis

Kenna¹,

Davidson²,

Thomas³

2011

AGG

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Abstract:The spondyloarthropathies are a group of arthritides which specifically target the spine and pelvis with ankylosing spondylitis (AS) being the most prevalent and debilitating of these conditions. Unique to AS is the progression to excessive uncontrolled bone formation following an initial inflammatory phase that can result in joint fusion and significant disability. Spondyloarthritis is estimated to affect 1%-2% of the population, twice as many as rheumatoid arthritis and thus constitutes a significant health problem. Currently AS pathogenesis is very poorly understood but recent large-scale genetics and gene expression profiling studies have identified some of the underlying mechanisms and pathways contributing to the disease. Genome-wide association studies have identified a number of candidate genes associated with AS sharing the same pathways which are now being targeted for therapeutic intervention. However, although such approaches can identify genes contributing to the disease process and are very informative as to disease aetiopathogenesis, they cannot profile the actual changes in gene/cell activity at any point in the disease process or possibly more importantly at specific sites. Such information is generated using expression profiling. A number of expression profiling studies have been undertaken in AS, looking at both circulating cells and tissues from affected joints. Although some common genes/pathways have been identified, overall the results to date have been somewhat disappointing due to differences in experimental design and tissue source as well as the low power of the studies. More recent better powered studies have shown some potential in developing gene expression profiling as a diagnostic tool in AS. True future success will rely on larger genetic and genomic studies and the combination of these datasets in eQTL studies requiring significant collaborative efforts. Such larger-scale approaches will also generate sufficient power to target specific disease stages and sites.

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“…So far, the antigen-presenting specificity is the only known feature of B27 to show such a correlation, since subtypes differentially associated with AS bind to distinct peptide subsets (25)(26)(27)(28).…”

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confidence: 99%

Similar cell surface expression of β₂‐microglobulin–free heavy chains by HLA–B27 subtypes differentially associated with ankylosing spondylitis

Vázquez

Castro

2005

Arthritis & Rheumatism

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Objective. To determine whether the cell surface features of HLA-B27 subtypes reported to be differentially associated with ankylosing spondylitis (AS) differ in a way that correlates with disease susceptibility.Methods. Human cell transfectants expressing or lacking the transporter associated with antigen processing were used to determine the cell surface expression of B27 subtypes by flow cytometry with antibodies recognizing the B27 heterodimer or ␤ 2 -microglobulin (␤ 2 m)-free heavy chains.Results. In lymphoid cells with an intact peptideloading complex, all B27 subtypes, irrespective of their association with disease, showed similar ratios of free heavy chain to heterodimer, suggesting similar surface stability. A substantial decrease in dissociated heavy chains, which never reached 100%, was observed upon addition of a B27 ligand, with no significant differences among subtypes. This is compatible with similar surface expression of irreversible ␤ 2 m-free heavy chain forms among subtypes differentially associated with disease. In cells lacking the transporter associated with antigen processing, both disease-associated and non-diseaseassociated subtypes expressed a population of heterodimers at 26°C that was less stable than the population expressed at 37°C. In the presence of exogenous peptide, the expression of heterodimers increased, without a concomitant decrease in ␤ 2 m-free heavy chains. This suggests that in these cells, and for all subtypes tested, most of the dissociated heavy chains at the cell surface are in irreversible forms. At 37°C, the expression of ␤ 2 m-free B27 heavy chains was very low on T2 transfectant cells. Conclusion. HLA-B27 subtypes showing differential associations with AS are similar in their extent of ␤ 2 m dissociation and surface expression of free heavy chains.Class I major histocompatibility complex (MHC) proteins are heterodimers consisting of a polymorphic heavy chain that is noncovalently bound to ␤ 2 -microglobulin (␤ 2 m), a nonpolymorphic polypeptide. Assembly of MHC molecules takes place in the endoplasmic reticulum (ER), where they constitutively bind peptides. These arise mainly from proteasomal degradation in the cytosol, are transported into the lumen of the ER by means of the transporter associated with antigen processing (TAP), and bind, sometimes after trimming, to the class I molecule in a process involving several proteins collectively known as the peptide-loading complex (1). Peptides bound with sufficient affinity stabilize the native conformation of the nascent class I molecule. When this happens, the peptide-MHC complex is released from the ER and traffics to the cell surface. In cells lacking TAP, the peptide supply into the ER and the expression of class I MHC are drastically reduced. However, at 26°C, MHC molecules that are presumably devoid of peptide can be sufficiently stable to leave the ER and reach the cell surface (2).The ␤ 2 m-free class I MHC polypeptides are found at the cell surface. This can be revealed, for example, by cell surface stain...

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Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Cited by 82 publications

References 69 publications

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

The genomics and genetics of ankylosing spondylitis

Similar cell surface expression of β₂‐microglobulin–free heavy chains by HLA–B27 subtypes differentially associated with ankylosing spondylitis

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Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Cited by 82 publications

References 69 publications

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

The genomics and genetics of ankylosing spondylitis

Similar cell surface expression of β2‐microglobulin–free heavy chains by HLA–B27 subtypes differentially associated with ankylosing spondylitis

Contact Info

Product

Resources

About

Similar cell surface expression of β₂‐microglobulin–free heavy chains by HLA–B27 subtypes differentially associated with ankylosing spondylitis