Inferring Epitopes of a Polymorphic Antigen Amidst Broadly Cross-Reactive Antibodies Using Protein Microarrays: a Study of OspC Proteins of Borrelia burgdorferi
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PROVIDER: PRJNA196868 | ENA |
REPOSITORIES: ENA
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Project description:Epitope mapping studies aim to identify the binding sites of antibody-antigen interactions to enhance the development of vaccines, diagnostics and immunotherapeutic compounds. However, mapping is a laborious process employing time- and resource-consuming M-bM-^@M-^Xwet benchM-bM-^@M-^Y techniques or epitope prediction software that are still in their infancy. For polymorphic antigens, another challenge is characterizing cross-reactivity between epitopes, teasing out distinctions between broadly cross-reactive responses, limited cross-reactions among variants and the truly type-specific responses. A refined understanding of cross-reactive antibody binding could guide the selection of the most informative subsets of variants for diagnostics and multivalent subunit vaccines. We explored the antibody binding reactivity of sera from human patients and Peromyscus leucopus rodents infected with Borrelia burgdorferi to the polymorphic outer surface protein C (OspC), an attractive candidate antigen for vaccine and improved diagnostics for Lyme disease. We constructed a protein microarray displaying 23 natural variants of OspC and quantified the degree of cross-reactive antibody binding between all pairs of variants, using Pearson correlation calculated on the reactivity values using three independent transforms of the raw data: (1) logarithmic, (2) rank, and (3) binary indicators. We observed that the global amino acid sequence identity between OspC pairs was a poor predictor of cross-reactive antibody binding. Then we asked if specific regions of the protein would better explain the observed cross-reactive binding and performed in silico screening of the linear sequence and 3-dimensional structure of OspC. This analysis pointed to the C-terminal helix of the structure as a major determinant of type-specific cross-reactive antibody binding. We developed bioinformatics methods to systematically analyze the relationship between local sequence/structure variation and cross-reactive antibody binding patterns among variants of a polymorphic antigen, and this method can be applied to other polymorphic antigens for which immune response data is available for multiple variants. Antibody profiling was performed on sera from Borrelia burgdorferi infected and non-infected humans and Peromyscus leucopus rodents against 23 variants of the surface protein OspC . For infected human serum samples, the OspC type of the infecting B. burgdorferi strain is unknown; for experimentally-infected P. leucopus serum samples, it is known. Of human serum samples, 55 were from infected individuals and 25 from naive controls. Of P. leucopus serum samples, 23 were from infected individuals and 7 were from naive controls.
2013-04-12 | E-GEOD-45996 | biostudies-arrayexpress
Project description:Epitope mapping studies aim to identify the binding sites of antibody-antigen interactions to enhance the development of vaccines, diagnostics and immunotherapeutic compounds. However, mapping is a laborious process employing time- and resource-consuming ‘wet bench’ techniques or epitope prediction software that are still in their infancy. For polymorphic antigens, another challenge is characterizing cross-reactivity between epitopes, teasing out distinctions between broadly cross-reactive responses, limited cross-reactions among variants and the truly type-specific responses. A refined understanding of cross-reactive antibody binding could guide the selection of the most informative subsets of variants for diagnostics and multivalent subunit vaccines. We explored the antibody binding reactivity of sera from human patients and Peromyscus leucopus rodents infected with Borrelia burgdorferi to the polymorphic outer surface protein C (OspC), an attractive candidate antigen for vaccine and improved diagnostics for Lyme disease. We constructed a protein microarray displaying 23 natural variants of OspC and quantified the degree of cross-reactive antibody binding between all pairs of variants, using Pearson correlation calculated on the reactivity values using three independent transforms of the raw data: (1) logarithmic, (2) rank, and (3) binary indicators. We observed that the global amino acid sequence identity between OspC pairs was a poor predictor of cross-reactive antibody binding. Then we asked if specific regions of the protein would better explain the observed cross-reactive binding and performed in silico screening of the linear sequence and 3-dimensional structure of OspC. This analysis pointed to the C-terminal helix of the structure as a major determinant of type-specific cross-reactive antibody binding. We developed bioinformatics methods to systematically analyze the relationship between local sequence/structure variation and cross-reactive antibody binding patterns among variants of a polymorphic antigen, and this method can be applied to other polymorphic antigens for which immune response data is available for multiple variants.
2013-04-12 | GSE45996 | GEO
Project description:Epitope mapping studies aim to identify the binding sites of antibody-antigen interactions to enhance the development of vaccines, diagnostics and immunotherapeutic compounds. However, mapping is a laborious process employing time- and resource-consuming 'wet bench' techniques or epitope prediction software that are still in their infancy. For polymorphic antigens, another challenge is characterizing cross-reactivity between epitopes, teasing out distinctions between broadly cross-reactive responses, limited cross-reactions among variants and the truly type-specific responses. A refined understanding of cross-reactive antibody binding could guide the selection of the most informative subsets of variants for diagnostics and multivalent subunit vaccines. We explored the antibody binding reactivity of sera from human patients and Peromyscus leucopus rodents infected with Borrelia burgdorferi to the polymorphic outer surface protein C (OspC), an attractive candidate antigen for vaccine and improved diagnostics for Lyme disease. We constructed a protein microarray displaying 23 natural variants of OspC and quantified the degree of cross-reactive antibody binding between all pairs of variants, using Pearson correlation calculated on the reactivity values using three independent transforms of the raw data: (1) logarithmic, (2) rank, and (3) binary indicators. We observed that the global amino acid sequence identity between OspC pairs was a poor predictor of cross-reactive antibody binding. Then we asked if specific regions of the protein would better explain the observed cross-reactive binding and performed in silico screening of the linear sequence and 3-dimensional structure of OspC. This analysis pointed to residues 179 through 188 the fifth C-terminal helix of the structure as a major determinant of type-specific cross-reactive antibody binding. We developed bioinformatics methods to systematically analyze the relationship between local sequence/structure variation and cross-reactive antibody binding patterns among variants of a polymorphic antigen, and this method can be applied to other polymorphic antigens for which immune response data is available for multiple variants.
| S-EPMC3691210 | biostudies-literature
Project description:see publication, arrays from 4 XXY genotypes containing polymorphic Y chromosomes
2010-10-02 | GSE23612 | GEO
Project description:Polymorphic immune mechanisms regulate commensal repertoire
| PRJNA562711 | ENA
Project description:We used customized peptide arrays of 163 TXNDC16 peptides to identify immunogenic TXNDC16 epitopes and asked whether discrimination of meningioma and control sera is possible with a specific subset selection of all immunogenic epitopes.
2014-07-01 | GSE58949 | GEO
Project description:Environmental influences such as infections and dietary changes strongly affect a host’s microbiota. In the steady state, however, host genetics may influence the microbiota composition, as suggested by the greater similarity between the microbiomes of identical twin pairs compared to non-identical twins. Understanding the role of polymorphic mechanisms in regulating the commensal communities is complicated by the variability of human genomes and microbiomes, and by microbial sensitivity to the environment. Animal studies allow genetic modifications, but are also sensitive to influences known as ‘cage’ or ‘legacy’ effects. Here, we analyzed ex-germ-free mice of various genetic backgrounds, including immunodeficient and Major Histocompatibility Complex (MHC)-congenic strains repopulated with identical input microbiota. We found that the host’s genetic polymorphic mechanisms did indeed affect the gut microbiome and that both innate (e.g. anti-microbial peptides, complement, pentraxins and enzymes affecting microbial survival), as well as adaptive (both MHC-dependent and MHC-independent) pathways influenced the microbiota. These polymorphic mechanisms regulated only a limited number of microbial lineages (independently of their abundance). In addition, our comparative analyses suggested that some microbes might benefit from the specific immune responses that they elicit.
2019-08-29 | GSE136572 | GEO
Project description:We used customized peptide arrays of 163 TXNDC16 peptides to identify immunogenic TXNDC16 epitopes and asked whether discrimination of meningioma and control sera is possible with a specific subset selection of all immunogenic epitopes. CelluSpotsM-bM-^DM-" peptide arrays were manufactured by Intavis (Germany) with 163 TXNDC16 spanning peptides spotted as two replicate subarrays. 15-mer peptides overlapping by 10 amino acids were covalently bound to cellulose membranes with their C-termini. Please note that the non_normalized.txt contains Ch1 Mean values for all samples (each sequence represented in duplicates) and the identifiers in the 'index' column corresponds to those in the 'index' column in raw gpr files; sample data table contains classification values (for each sequence) described in the sample data processing field.
2014-07-01 | E-GEOD-58949 | biostudies-arrayexpress
Project description:see publication, arrays from 4 XXY genotypes containing polymorphic Y chromosomes Dye swaps, loop design.
2010-10-02 | E-GEOD-23612 | biostudies-arrayexpress
Project description:We report the transcriptome data produced from isogenic polymorphic p53 codon 72 iPSCs under doxorubicin treatment. By inserting BAC DNA into one allele of the heterozygous polymorphic p53 codon 72, each clone expressed a p53 protein encoding P72 or R72 from another allele in which it was not inserted. The transcriptional regulation of p53 target genes was compared between the isogenic lines under doxorubicin treatment.
2021-09-10 | GSE183668 | GEO