Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis

Lorente, Elena; Redondo-Antón, Jennifer; Martín-Esteban, Adrián; Guasp, Pablo; Barnea, Eilon; Lauzurica, Pilar; Admon, Arie; Castro, José A. Łópez de

doi:10.1074/mcp.ra119.001710

Cited by 9 publications

(6 citation statements)

References 40 publications

(60 reference statements)

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“…Positive HLA-B*40:02 binding has been established for the human PAM peptide ("KEPGSGVPVVL") and the ANXA7 peptide ("VESGLKTIL") [15][16][17] , that contain the distinctive mimicking SARS-CoV-2 peptides ( Table 1). The closely related HLA-B*40:01 allele also binds this mimicked ANXA7 peptide 17 .…”

Section: Resultsmentioning

confidence: 99%

Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2

et al. 2020

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The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we report 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and the human reference proteome. We benchmark this observation against other viral–human 8-mer/9-mer peptide identity, which suggests generally similar extents of molecular mimicry for SARS-CoV-2 and many other human viruses. Interestingly, 20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS). Furthermore, four of the human 8-mer/9-mer peptides mimicked by SARS-CoV-2 map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by single-cell RNA-seq (scRNA-seq) analysis that shows the targeted genes significantly expressed in human lungs and arteries; tissues implicated in COVID-19 pathogenesis. Finally, HLA-A*03 restricted 8-mer peptides are found to be shared broadly by human and coronaviridae helicases in functional hotspots, with potential implications for nucleic acid unwinding upon initial infection. This study presents the first scan of human peptide mimicry by SARS-CoV-2, and via its benchmarking against human–viral mimicry more broadly, presents a computational framework for follow-up studies to assay how evolutionary tinkering may relate to zoonosis and herd immunity.

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Section: Resultsmentioning

confidence: 99%

Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2

et al. 2020

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“…Moreover, ESGLKTIL was also found within a 9-meric epitope of SARS-CoV-2, which is known as an HLA-B*40:01 binder. Although HLA-B*40:01 and HLA-B*40:02 are protective for autoimmune hepatitis ( 87 ), these alleles are associated with ankylosing spondylitis (AS) ( 88 , 89 ). Ankylosing spondylitis is associated with SARS-CoV-2 ( 76 ).Besides, positive experimental assays revealed that ESGLKTIL shares sequence identity (more than 90%) with 11-meric and 16-meric peptides from phosphoglycolate phosphatase.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Proteome Harbors Peptides Which Are Able to Trigger Autoimmunity Responses: Implications for Infection, Vaccination, and Population Coverage

et al. 2021

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Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.

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“…Moreover, as HLA class I molecules can accommodate longer peptides in their peptide binding cleft [ 112 , 113 , 114 ], ERAP1 polymorphisms that alter protein levels and activity result in the presentation of a different set of ligands in an HLA-B*27 background and, consequently, altered antigenicity. Consistent with the notion that altered peptide characteristics underlie disease pathogenesis, a loss-of-function ERAP2 variant that is associated with AS does not affect MHC class I surface levels, endoplasmic reticulum stress, or inflammatory cytokines production [ 98 , 115 ], but alters the peptidome available for MHC class I presentation [ 116 , 117 ].…”

Section: Models Of Spa Pathogenesis: Hypothesesmentioning

confidence: 96%

Understanding the Pathogenesis of Spondyloarthritis

Sharip

Kunz

2020

Biomolecules

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Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

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Substantial Influence of ERAP2 on the HLA-B40:02 Peptidome: Implications for HLA-B27-Negative Ankylosing Spondylitis

Cited by 9 publications

References 40 publications

Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2

Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2

SARS-CoV-2 Proteome Harbors Peptides Which Are Able to Trigger Autoimmunity Responses: Implications for Infection, Vaccination, and Population Coverage

Understanding the Pathogenesis of Spondyloarthritis

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