p185, an Immunodominant Epitope, Is an Autoantigen Mimotope

Kumar, Sanjeev; Hinks, John A.; Maman, Joseph D.; Ravirajan, C. T.; Pearl, Laurence H.; Isenberg, David

doi:10.1074/jbc.m111.224303

Cited by 6 publications

(4 citation statements)

References 53 publications

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“…Such displacement causes R-loop prone regions to contain multiple polynucleotide structures: double stranded DNA, single stranded DNA, RNA:DNA hybrids, single stranded RNA (reviewed in [16]), G quadruplex complexes [30,31], etc., all of which can be bound by antibodies with a range of affinities [30,[32][33][34][35]. Anti-DNA antibodies are abundant in the serum of normal animals immunized with protein fragments [36][37][38][39][40][41][42][43][44][45], and are frequently polyspecific [40,[46][47][48][49][50][51][52][53][54] -they can bind both polynucleotide and non-polynucleotide (e.g. peptide, phospholipid) epitopes [35].…”

Section: Discussionmentioning

confidence: 99%

HOT or not: examining the basis of high-occupancy target regions

Wreczycka

Franke

Uyar

et al. 2017

Preprint

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High-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed 'hyper-ChIPable' regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpGrich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (Gquadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

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Section: Discussionmentioning

confidence: 99%

HOT or not: examining the basis of high-occupancy target regions

Wreczycka

Franke

Uyar

et al. 2017

Preprint

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“…After binding to its antibody, tumor growth is significantly inhibited. Still, there is also a part of the antigen-antibody binding that reduces the immune system’s ability to recognize tumor antigens, increasing the possibility of immune escape 32 .…”

Section: Tumor Immune Surveillance Under the Influence Of Smokingmentioning

confidence: 99%

The effect of smoking on tumor immunoediting: Friend or foe?

Jiang,

2024

Tob. Induc. Dis.

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“…In our study the predicted peptides were discontinuous and were from subdomain III of HER2 ECD. Kumar et al (2011) reported the peptide p185 (378-394) (PESFDGDPASNTAPLQPE), which encompasses several segments (S75, S76, S77, and S78) of HER2 ECD subdomain III shown in Table 1, as an immunodominant auto antigen mimotope possibly serving as an antigenic stimulus to trigger systemic lupus erythematosus in a subset of patients. Thus, it presents a potential safety issue for prospective vaccine development of constructs containing the said segments.…”

Section: Figure 2 Predicted Structures Of B-cell Epitope Peptides Anmentioning

confidence: 99%

In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines

Mahdavi

Keyhanfar²,

Moreau³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

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p185, an Immunodominant Epitope, Is an Autoantigen Mimotope

Cited by 6 publications

References 53 publications

HOT or not: examining the basis of high-occupancy target regions

HOT or not: examining the basis of high-occupancy target regions

The effect of smoking on tumor immunoediting: Friend or foe?

In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines

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