Hla-B27

Bowness, Paul

doi:10.1146/annurev-immunol-032414-112110

Cited by 218 publications

(190 citation statements)

References 107 publications

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“…1 T cell response primed by cross-reactive microbial antigen(s), thus breaking selftolerance and perpetuating an autoimmune process leading to tissue damage [9]. In accordance with this hypothesis, HLA-B27-restricted CD8 1 T cells reactive against both selfpeptides and enterobacterial antigens were found in the synovial fluid of patients with AS and ReA [10].…”

Section: Introductionmentioning

confidence: 67%

“…First, the HLA-B27 displays an altered folding rate during the assembly into the ER [9,21,22]. This misfolding is a consequence of the particularly slow HLA-B27 maturation rate that triggers the endoplasmic reticulum (ER)-associated degradation (ERAD) of the heavy chains [22].…”

Section: Introductionmentioning

confidence: 99%

“…Another peculiarity of the HLA-B27 is related to its expression on the cell surface as a non-canonical form made by b2m-free homodimers [9,21,28]. The formation of homodimers arises from endosomal recycling compartments and is caused by the impaired and highly reactive cysteine 67 (Cys67) located into the B pocket of the peptide groove [29].…”

Section: Introductionmentioning

confidence: 99%

“…A pivotal role has been ascribed to residues 114 and 116 located in the F pocket of the binding groove, which notoriously influence the repertoire of bound peptides but also chaperone association, assembly process, maturation rate and, lastly, heavy chain dimerization [43,44]. Interestingly, these residues distinguish the AS-associated from the non-AS-associated alleles [9,16]. Of note, Tyr116 in B*2706, much more than His116 in B*2709, appears to impact positively on the assembly kinetics, thus reducing dimer formation [44].…”

Section: Introductionmentioning

confidence: 99%

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The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis

Vitulano

Tedeschi

Paladini

et al. 2017

Clinical and Experimental Immunology

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1These authors contributed equally to this study. SummaryThe human leukocyte antigen class I gene HLA-B27 is the strongest risk factor for ankylosing spondylitis (AS), a chronic inflammatory arthritic disorder. More recently, the Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 genes have been identified by genome wide association studies (GWAS) as additional susceptibility factors. In the ER, these aminopeptidases trim the peptides to a length suitable to fit into the groove of the major histocompatibility complex (MHC) class I molecules. It is noteworthy that an epistatic interaction between HLA-B27 and ERAP1, but not between HLA-B27 and ERAP2, has been highlighted. However, these observations suggest a paramount centrality for the HLA-B27 peptide repertoire that determines the natural B27 immunological function, i.e. the T cell antigen presentation and, as a by-product, elicits HLA-B27 aberrant behaviours: (i) the misfolding leading to ER stress responses and autophagy and (ii) the surface expression of homodimers acting as ligands for innate immune receptors. In this context, it has been observed that the HLA-B27 carriers, besides being prone to autoimmunity, display a far better surveillance to some viral infections. This review focuses on the ambivalent role of HLA-B27 in autoimmunity and viral protection correlating its functions to the quantitative and qualitative effects of ERAP1 and ERAP2 polymorphisms on their enzymatic activity.

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Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis

Vitulano

Tedeschi

Paladini

et al. 2017

Clinical and Experimental Immunology

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“…The structure of MHC-I H-chain only dimers are also unclear, but there are global differences in the fold, and likely the dimer alters accessibility to the a3 domain. The strong association between HLA-B27 and spondyloarthropathies inspired models of how the interaction between misfolded soluble HLA-B27 and LILRB2 could trigger inflammation (32). Alternatively, because the activating LILRA1 also interacts with B27, it might be involved in promoting responses.…”

Section: Nonconventional Mhc-i Ligandsmentioning

confidence: 99%

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Burshtyn

Morcos

2016

The Journal of Immunology

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The human leukocyte Ig-like receptor family is part of the paired receptor system. The receptors are widely expressed by various immune cells, and new functions continue to emerge. Understanding the range of functions of the receptors is of general interest because several types of pathogens exploit the receptors and genetic diversity of the receptors has been linked to various autoimmune diseases. Class I major histocompatibility molecules were the first ligands appreciated for these receptors, but the types of ligands identified over the last several years are quite diverse, including intact pathogens, immune-modulatory proteins, and molecules normally found within the CNS. This review focuses on the types of ligands described to date, how the individual receptors bind to several distinct types of ligands, and the known functional consequences of those interactions.

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Molecular Genetics of Ankylosing Spondylitis

Smith

2016

Encyclopedia of Life Sciences

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Ankylosing spondylitis (AS) is a chronic immune‐mediated arthritic condition affecting the spine that can result in disabling fusion of the vertebrae and sacroiliac joints. Genetics plays a more dominant role in conferring risk for AS than in most autoimmune diseases, as evidenced by a heritability greater than 90%. The HLA‐B*27 gene allele represents the greatest single risk factor identified to date, and multiple theories have been proposed to explain its contribution to pathogenesis. Genomewide association studies in AS have revealed other key genetic players, such as the polymorphic ERAP1 , and implicated specific immune pathways, notably the IL‐23/IL17 cytokine pathway. However, much of the genetic basis for AS remains to be explained, providing future challenges to researchers and hope for clinicians. Key Concepts Ankylosing spondylitis belongs to a group of related inflammatory conditions typified by spinal arthritis, extraarticular inflammation and high prevalence of the MHC class I allele HLA‐B*27. Ankylosing spondylitis has unusually high heritability, suggesting a strong genetic basis. HLA‐B*27 remains the greatest genetic risk factor identified to date. Multiple theories have been proposed to explain the link between HLA‐B*27 and disease ranging from immune recognition at the cell surface to unusual characteristics of its biosynthesis. Genomewide association studies (GWAS) have identified other MHC genes, non‐MHC key molecules and immune pathways that contribute to ankylosing spondylitis. The relevance of one of the GWAS pathways, the IL‐23/IL‐17 pathway, has borne out in treatment efficacy of related monoclonal antibody therapy in patients. The genetic overlap between ankylosing spondylitis, inflammatory bowel disease and psoriasis may explain the frequently observed gut and skin inflammation comorbidities in ankylosing spondylitis. Most of the ankylosing spondylitis heritability (about 70%) remains unexplained.

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Hla-B27

Cited by 218 publications

References 107 publications

The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis

The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Molecular Genetics of Ankylosing Spondylitis

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