ERAP1 reduces accumulation of aberrant and disulfide-linked forms of HLA-B27 on the cell surface

Tran, Tri M.; Hong, Seok Il; Edwan, Jehad H.; Colbert, Robert A.

doi:10.1016/j.molimm.2016.04.002

Cited by 23 publications

(25 citation statements)

References 49 publications

(82 reference statements)

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“…Except CNX and ERAP1, all APM knockouts induced a significant decrease of HLA-I surface expression confirming findings of others. ERAP1 knockout cells show a slight but significant increase in surface HLA-I, which has been observed before(20). The chaperones CALR and CNX are known to execute similar functions(21).…”

Section: Resultssupporting

confidence: 83%

PAKC: A novel Panel of HLA class I Antigen presentation machinery Knockout Cells from the same genetic origin

Waard

Verkerk

Jongsma

et al. 2020

Preprint

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With the emergence of immunotherapies, the understanding of functional HLA class I antigen presentation to T cells is more relevant than ever. Current knowledge on antigen presentation is based on decades of research in a wide variety of cell types with varying antigen presentation machinery (APM) expression patterns, proteomes and HLA haplotypes. This diversity complicates the establishment of individual APM contributions to antigen generation, selection and presentation. Therefore, we generated a novel Panel of APM Knockout Cell lines (PAKC) from the same genetic origin. After CRISPR/Cas9 genome-editing of ten individual APM components in a human cell line, we derived clonal cell lines and confirmed their knockout status and phenotype. We then show how PAKC will accelerate research on the functional interplay between APM components and their role in antigen generation and presentation. This will lead to improved understanding of peptide-specific T cell responses in infection, cancer and autoimmunity.Key pointsWe generated a panel of cell lines to study HLA class I antigen presentationWe show how this will spark research in infection, tumor biology and autoimmunity

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Section: Resultssupporting

confidence: 83%

PAKC: A novel Panel of HLA class I Antigen presentation machinery Knockout Cells from the same genetic origin

Waard

Verkerk

Jongsma

et al. 2020

Preprint

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“…Another report showed an opposite effect with a selective increase of FHC for AS-associated B*2705 and B*2704 subtypes but not for non-AS-associated B*2706 and B*2709 alleles on C1R transfectants [93]. Similarly, Tran and co-workers have observed an accumulation of disulphide-linked HLA-B27 dimers on U937 monocytic cell lines following ERAP1 knock-down, while levels of HLA-B18 and HLA-B51 were unaffected [94].…”

Section: Hla-b27 and Erap1/2 As Players In Ankylosing Spondylitismentioning

confidence: 92%

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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“…4a). The evidence linking specific 130,131 . These observations highlight the difficulties with extrapolating data from cell lines overexpressing HLA-B27 to disease.…”

Section: [H1] Mechanisms Of Hla Disease Associationsmentioning

confidence: 99%

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

2019

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Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA genotype with other genes and environmental risk factors in determining disease risk have been identified. This Review provides basic information on the genetics and molecular function of HLA molecules, as well as general features of HLA associations with disease. We summarise evidence for various peptidedependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis: rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and pediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases. [ED: Some general editorial comments are replied to in the marginal comments. For replies to reviewers, please see the accompanying file.]

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ERAP1 reduces accumulation of aberrant and disulfide-linked forms of HLA-B27 on the cell surface

Cited by 23 publications

References 49 publications

PAKC: A novel Panel of HLA class I Antigen presentation machinery Knockout Cells from the same genetic origin

PAKC: A novel Panel of HLA class I Antigen presentation machinery Knockout Cells from the same genetic origin

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

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

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