Epitopes

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Ying Hua Chen - One of the best experts on this subject based on the ideXlab platform.

  • ELNKWA-epitope specific antibodies induced by epitope-vaccine recognize ELDKWA- and other two neutralizing-resistant mutated Epitopes on HIV-1 gp41.
    Immunology letters, 2001
    Co-Authors: Xiao Nan Dong, Yi Xiao, Ying Hua Chen
    Abstract:

    Based on the fact that monoclonal antibody (mAb) 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 separately or in combination with other mAbs showed potent neutralizing activity to a wide range of primary HIV-1 isolates in vivo and in vitro, but this epitope undergoes restricted mutation. ELNKWA is a neutralizing-resistant mutated epitope. We induced ELNKWA-epitope-specific polyclonal and monoclonal antibodies and studied the interaction of the antibodies with ELDKWA-epitope and other two neutralizing-resistant mutated Epitopes. The candidate ELNKWA-epitope-vaccine induced a high level of antibodies to the ELNKWA-epitope-peptide. The ELNKWA-epitope-specific polyclonal antibodies bound not only the ELNKWA-, but also ELDKWA-, ELEKWA- and ELDEWA-epitope-peptides in ELISA-assay. Moreover, the antibodies also recognized four C-domain-peptides (P5, P6, P7, P8) which contain these four Epitopes, respectively. Interestingly, an ELNKWA-epitope-specific monoclonal antibody (TH-Ab1) induced by the candidate ELNKWA-epitope-vaccine could also recognize the four C-domain-peptides containing ELNKWA-, ELDKWA-, ELEKWA- and ELDEWK-Epitopes. These results indicate that the candidate ELNKWA-epitope-vaccine could induce high levels of antibodies, which recognize the neutralizing epitope ELDKWA and three neutralizing-resistant mutated Epitopes, suggesting that the candidate ELNKWA-epitope-vaccine may help to overcome the problem of viral escape from neutralization through mutation at D or K position, and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1.

  • HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies
    International immunopharmacology, 2001
    Co-Authors: Haijun Tian, Yi Xiao, Mei Zhu, Ying Hua Chen
    Abstract:

    Abstract Some neutralizing Epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro. But only very low levels of antibodies to these Epitopes were determined in the HIV-1 infected individuals. In this study, the aluminum (alum) adjuvant to increase the immunogenicity of the neutralizing Epitopes was used. Three epitope-peptides [C-(ELDKWAG)4, C-(RILAVERYLKD-G)2 and C-(GPGRAFY)2], which contain three Epitopes (ELDKWA, RILAVERYLKD, GPGRAFY) from the HIV-1 Env proteins, were synthesized and conjugated to carrier protein keyhole limpet hemocyanin (KLH). The epitope-vaccines C-(ELDKWAG)4-KLH and C-(RILAVERYLKD-G)2-KLH in alum induced high levels of epitope-specific antibodies recognizing the Epitopes from epitope-peptides C-(ELDKWAG)4 and C-(RILAVERYLKD-G)2, as well as the gp41 C-domain peptides P2 [C-TSLIHSLIEESQNQQEKNEQELLELDKWA (aa 646–674)] and P1 [LQARILAVERYLKDQQL (aa 583–599)] and the recombinant soluble gp41 (rsgp41) bearing both Epitopes (antibody titer in rabbit sera was 1:12800–25,600 dilution). Immunoblotting analysis demonstrated that the antibodies in both antisera bound to rsgp41, indicating that both antibodies recognized the natural Epitopes on rsgp41 protein. The epitope-vaccines C-(GPGRAFY)2-KLH induced moderate GPGRAFY epitope-specific antibody response with a titer of 1:6400. In contrast, as it was demonstrated in previous studies, the immunization with rgp160 induced weak antibody response to these three Epitopes (titer of 1:400–1600). This suggests that epitope-peptides conjugated to KLH when infected with alum significantly increases immunogenicity of gp41 neutralizing Epitopes providing a hope for the development of an HIV-1 vaccine.

  • Antigenicity and predefined specificities of the multi-epitope vaccine in candidate consisting of neutralizing epitope and mutated Epitopes suggested a new way against HIV-1 mutation.
    Immunobiology, 2001
    Co-Authors: Haijun Tian, Yi Xiao, Li Qin, Ying Hua Chen
    Abstract:

    Summary A seven-amino acid epitope GPGRAFY located inside the V3 loop on envelope protein gp120 of HIV-1 is the principal neutralizing epitope (PNE), and a subset of anti-V3 antibodies specific for this epitope show a broad range of neutralizing activity. But this epitope undergoes restricted mutation. In this study, three epitope peptides [C-(GPGRAFY)2, C-(GPGQTFY)2 and C-(GPGQAWY)2] that contain neutralizing epitope GPGRAFY and its two mutated epitope GPGQTFY and GPGQAWY, were synthesized and then conjugated to carrier protein KLH (keyhole limpet hemocyanin). The epitope-vaccines C-(GPGRAFY)2-KLH, C-(GPGQTFY)2-KLH and C-(GPGQAWY)2-KLH induced high levels of antibodies to three V3 loop peptides that contain these Epitopes respectively, and the antibody response induced by each epitope-vaccine showed predefined epitope-specific. When these three epitope-peptides mixed together and conjugated to carrier protein, or conjugated to carrier protein separately and then mixed together, high levels of epitope-specific antibodies which respectively recognized these Epitopes on V3 loop peptide and both mutated peptides all can be induced by both of them. In blotting assay, these epitope-specific antibodies all recognized the neutralizing epitope and mutated Epitopes on peptides respectively. In addition, the reactivity of the antibodies with whole gp120 molecule which contained the epitope GPGRAFY was tested. Only the GPGRAFY-epitope-specific antibodies but not the other antibodies recognized the gp120 molecule. These results provide experimental evidence that the candidate multi-epitope-vaccine containing neutralizing epitope and mutated Epitopes may bring new hope against viral mutation resulting in HIV-1 immune evasion and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1 infection.

  • Induction of high levels of antibodies recognizing the neutralizing epitope ELDKWA and the D- or K-position-mutated Epitopes by candidate epitope vaccines against HIV-1.
    International archives of allergy and immunology, 2000
    Co-Authors: Yi Xiao, Xiao Nan Dong, Ying Hua Chen
    Abstract:

    Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a significant neutralization potency against 90% of the investigated viruses of African, Asian, American, and European strains, but the antibody responses to the epitope 2F5 in HIV-1-infected individuals were very low. We attempted to induce high levels of epitope-specific antibodies to ELDKWA and its three mutated Epitopes by candidate epitope vaccines. The four candidate epitope vaccines all induced strong antibody responses at dilutions from about 1:6,400 to 1:25,600. We tested the cross-reactions between these antisera and four epitope peptides. The ELDKWA-specific antisera showed strong cross-reactivity with three neutralizing-resistant mutated Epitopes which contain changes in the D or K positions of the epitope sequence. Virus variants containing these changes could escape neutralization by monoclonal antibody 2F5. In immunoblotting analysis, the ELDKWA, ELDEWA, and ELEKWA epitope specific antibodies all recognized rsgp41 which confirms that the antibodies against both mutated Epitopes, ELDEWA and ELEKWA, could cross-react with the native epitope on rsgp41. Although it is not clear whether the polyclonal antibodies induced by the ELDKWA epitope vaccine could neutralize the mutated viruses containing these mutated Epitopes, it is conceivable that epitope vaccines based on mutated Epitopes could induce strong antibody responses with predefined epitope specificity to neutralize mutated viruse containing the mutated epitope. An epitope vaccine, using different Epitopes including mutated Epitopes, could provide a new concept for developing a new vaccine against HIV-1.

Yi Xiao - One of the best experts on this subject based on the ideXlab platform.

  • ELNKWA-epitope specific antibodies induced by epitope-vaccine recognize ELDKWA- and other two neutralizing-resistant mutated Epitopes on HIV-1 gp41.
    Immunology letters, 2001
    Co-Authors: Xiao Nan Dong, Yi Xiao, Ying Hua Chen
    Abstract:

    Based on the fact that monoclonal antibody (mAb) 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 separately or in combination with other mAbs showed potent neutralizing activity to a wide range of primary HIV-1 isolates in vivo and in vitro, but this epitope undergoes restricted mutation. ELNKWA is a neutralizing-resistant mutated epitope. We induced ELNKWA-epitope-specific polyclonal and monoclonal antibodies and studied the interaction of the antibodies with ELDKWA-epitope and other two neutralizing-resistant mutated Epitopes. The candidate ELNKWA-epitope-vaccine induced a high level of antibodies to the ELNKWA-epitope-peptide. The ELNKWA-epitope-specific polyclonal antibodies bound not only the ELNKWA-, but also ELDKWA-, ELEKWA- and ELDEWA-epitope-peptides in ELISA-assay. Moreover, the antibodies also recognized four C-domain-peptides (P5, P6, P7, P8) which contain these four Epitopes, respectively. Interestingly, an ELNKWA-epitope-specific monoclonal antibody (TH-Ab1) induced by the candidate ELNKWA-epitope-vaccine could also recognize the four C-domain-peptides containing ELNKWA-, ELDKWA-, ELEKWA- and ELDEWK-Epitopes. These results indicate that the candidate ELNKWA-epitope-vaccine could induce high levels of antibodies, which recognize the neutralizing epitope ELDKWA and three neutralizing-resistant mutated Epitopes, suggesting that the candidate ELNKWA-epitope-vaccine may help to overcome the problem of viral escape from neutralization through mutation at D or K position, and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1.

  • HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies
    International immunopharmacology, 2001
    Co-Authors: Haijun Tian, Yi Xiao, Mei Zhu, Ying Hua Chen
    Abstract:

    Abstract Some neutralizing Epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro. But only very low levels of antibodies to these Epitopes were determined in the HIV-1 infected individuals. In this study, the aluminum (alum) adjuvant to increase the immunogenicity of the neutralizing Epitopes was used. Three epitope-peptides [C-(ELDKWAG)4, C-(RILAVERYLKD-G)2 and C-(GPGRAFY)2], which contain three Epitopes (ELDKWA, RILAVERYLKD, GPGRAFY) from the HIV-1 Env proteins, were synthesized and conjugated to carrier protein keyhole limpet hemocyanin (KLH). The epitope-vaccines C-(ELDKWAG)4-KLH and C-(RILAVERYLKD-G)2-KLH in alum induced high levels of epitope-specific antibodies recognizing the Epitopes from epitope-peptides C-(ELDKWAG)4 and C-(RILAVERYLKD-G)2, as well as the gp41 C-domain peptides P2 [C-TSLIHSLIEESQNQQEKNEQELLELDKWA (aa 646–674)] and P1 [LQARILAVERYLKDQQL (aa 583–599)] and the recombinant soluble gp41 (rsgp41) bearing both Epitopes (antibody titer in rabbit sera was 1:12800–25,600 dilution). Immunoblotting analysis demonstrated that the antibodies in both antisera bound to rsgp41, indicating that both antibodies recognized the natural Epitopes on rsgp41 protein. The epitope-vaccines C-(GPGRAFY)2-KLH induced moderate GPGRAFY epitope-specific antibody response with a titer of 1:6400. In contrast, as it was demonstrated in previous studies, the immunization with rgp160 induced weak antibody response to these three Epitopes (titer of 1:400–1600). This suggests that epitope-peptides conjugated to KLH when infected with alum significantly increases immunogenicity of gp41 neutralizing Epitopes providing a hope for the development of an HIV-1 vaccine.

  • Antigenicity and predefined specificities of the multi-epitope vaccine in candidate consisting of neutralizing epitope and mutated Epitopes suggested a new way against HIV-1 mutation.
    Immunobiology, 2001
    Co-Authors: Haijun Tian, Yi Xiao, Li Qin, Ying Hua Chen
    Abstract:

    Summary A seven-amino acid epitope GPGRAFY located inside the V3 loop on envelope protein gp120 of HIV-1 is the principal neutralizing epitope (PNE), and a subset of anti-V3 antibodies specific for this epitope show a broad range of neutralizing activity. But this epitope undergoes restricted mutation. In this study, three epitope peptides [C-(GPGRAFY)2, C-(GPGQTFY)2 and C-(GPGQAWY)2] that contain neutralizing epitope GPGRAFY and its two mutated epitope GPGQTFY and GPGQAWY, were synthesized and then conjugated to carrier protein KLH (keyhole limpet hemocyanin). The epitope-vaccines C-(GPGRAFY)2-KLH, C-(GPGQTFY)2-KLH and C-(GPGQAWY)2-KLH induced high levels of antibodies to three V3 loop peptides that contain these Epitopes respectively, and the antibody response induced by each epitope-vaccine showed predefined epitope-specific. When these three epitope-peptides mixed together and conjugated to carrier protein, or conjugated to carrier protein separately and then mixed together, high levels of epitope-specific antibodies which respectively recognized these Epitopes on V3 loop peptide and both mutated peptides all can be induced by both of them. In blotting assay, these epitope-specific antibodies all recognized the neutralizing epitope and mutated Epitopes on peptides respectively. In addition, the reactivity of the antibodies with whole gp120 molecule which contained the epitope GPGRAFY was tested. Only the GPGRAFY-epitope-specific antibodies but not the other antibodies recognized the gp120 molecule. These results provide experimental evidence that the candidate multi-epitope-vaccine containing neutralizing epitope and mutated Epitopes may bring new hope against viral mutation resulting in HIV-1 immune evasion and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1 infection.

  • Induction of high levels of antibodies recognizing the neutralizing epitope ELDKWA and the D- or K-position-mutated Epitopes by candidate epitope vaccines against HIV-1.
    International archives of allergy and immunology, 2000
    Co-Authors: Yi Xiao, Xiao Nan Dong, Ying Hua Chen
    Abstract:

    Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a significant neutralization potency against 90% of the investigated viruses of African, Asian, American, and European strains, but the antibody responses to the epitope 2F5 in HIV-1-infected individuals were very low. We attempted to induce high levels of epitope-specific antibodies to ELDKWA and its three mutated Epitopes by candidate epitope vaccines. The four candidate epitope vaccines all induced strong antibody responses at dilutions from about 1:6,400 to 1:25,600. We tested the cross-reactions between these antisera and four epitope peptides. The ELDKWA-specific antisera showed strong cross-reactivity with three neutralizing-resistant mutated Epitopes which contain changes in the D or K positions of the epitope sequence. Virus variants containing these changes could escape neutralization by monoclonal antibody 2F5. In immunoblotting analysis, the ELDKWA, ELDEWA, and ELEKWA epitope specific antibodies all recognized rsgp41 which confirms that the antibodies against both mutated Epitopes, ELDEWA and ELEKWA, could cross-react with the native epitope on rsgp41. Although it is not clear whether the polyclonal antibodies induced by the ELDKWA epitope vaccine could neutralize the mutated viruses containing these mutated Epitopes, it is conceivable that epitope vaccines based on mutated Epitopes could induce strong antibody responses with predefined epitope specificity to neutralize mutated viruse containing the mutated epitope. An epitope vaccine, using different Epitopes including mutated Epitopes, could provide a new concept for developing a new vaccine against HIV-1.

Teresa P. Dilorenzo - One of the best experts on this subject based on the ideXlab platform.

  • T Cell Epitopes and Neo-Epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal
    2020
    Co-Authors: Ada Admin, Eddie A. James, Roberto Mallone, Sally C. Kent, Teresa P. Dilorenzo
    Abstract:

    The autoimmune disease type 1 diabetes is characterized by effector T cell responses to pancreatic beta cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to beta cell demise and insulin insufficiency. Although a given HLA molecule presents a vast array of peptides, only those recognized by T cells are designated as Epitopes. Given their intimate link to etiology, the discovery and characterization of T cell Epitopes is a critical aspect of type 1 diabetes research. Understanding epitope recognition is also crucial for the pursuit of antigen-specific immunotherapies and implementation of strategies for T cell monitoring. For these reasons, a cataloging and appraisal of the T cell Epitopes targeted in type 1 diabetes was completed over a decade ago, providing an important resource for both the research and the clinical communities. Here we present a much-needed update and reappraisal of this earlier work, and include an online appendix that cross-indexes each epitope with its primary references and Immune Epitope Database (IEDB) identifier. Our analysis includes a grading scale to score the degree of evidence available for each epitope, which conveys our perspective on several useful criteria for epitope evaluation. While providing an efficient summary of the arguably impressive current state of knowledge, this work also brings to light several deficiencies. These include the need for improved epitope validation, as few Epitopes score highly by the criteria employed, and the dearth of investigations of the Epitopes recognized in the context of several under-studied type 1 diabetes-associated HLA molecules.

  • T-Cell Epitopes and Neo-Epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal.
    Diabetes, 2020
    Co-Authors: Eddie A. James, Roberto Mallone, Sally C. Kent, Teresa P. Dilorenzo
    Abstract:

    The autoimmune disease type 1 diabetes is characterized by effector T-cell responses to pancreatic β-cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to β-cell demise and insulin insufficiency. Although a given HLA molecule presents a vast array of peptides, only those recognized by T cells are designated as Epitopes. Given their intimate link to etiology, the discovery and characterization of T-cell Epitopes is a critical aspect of type 1 diabetes research. Understanding epitope recognition is also crucial for the pursuit of antigen-specific immunotherapies and implementation of strategies for T-cell monitoring. For these reasons, a cataloging and appraisal of the T-cell Epitopes targeted in type 1 diabetes was completed over a decade ago, providing an important resource for both the research and the clinical communities. Here we present a much needed update and reappraisal of this earlier work and include online supplementary material where we cross-index each epitope with its primary references and Immune Epitope Database (IEDB) identifier. Our analysis includes a grading scale to score the degree of evidence available for each epitope, which conveys our perspective on several useful criteria for epitope evaluation. While providing an efficient summary of the arguably impressive current state of knowledge, this work also brings to light several deficiencies. These include the need for improved epitope validation, as few Epitopes score highly by the criteria employed, and the dearth of investigations of the Epitopes recognized in the context of several understudied type 1 diabetes-associated HLA molecules.

Yuan-ding Chen - One of the best experts on this subject based on the ideXlab platform.

  • Immunoreactivity of chimeric proteins carrying poliovirus Epitopes on the VP6 of rotavirus as a vector
    Molecular Biology, 2016
    Co-Authors: Xiaoxia Pan, Bingxin Zhao, Yumei Teng, W.-y. Xia, Jianwei Wang, G.-y. Liao, C. Yang, Yuan-ding Chen
    Abstract:

    Rotavirus and poliovirus continue to present significant risks and burden of disease to children in developing countries. Developing a combined vaccine may effectively prevent both illnesses and may be advantageous in terms of maximizing compliance and vaccine coverage at the same visit. Recently, we sought to generate a vaccine vector by incorporating multiple Epitopes into the rotavirus group antigenic protein, VP6. In the present study, a foreign epitope presenting a system using VP6 as a vector was created with six sites on the outer surface of the vector that could be used for insertion of foreign Epitopes, and three VP6-based PV1 epitope chimeric proteins were constructed. The chimeric proteins were confirmed by immunoblot, immunofluorescence assay, and injected into guinea pigs to analyze the epitope-specific humoral response. Results showed that these chimeric proteins reacted with anti-VP6F and -PV1 antibodies, and elicited antibodies against both proteins in guinea pigs. Antibodies against the chimeric proteins carrying PV1 Epitopes neutralized rotavirus Wa and PV1 infection in vitro. Our study contributes to a better understanding of the use of VP6-based vectors as multiple-epitope delivery vehicles and the Epitopes displayed in this form could be considered for development of epitope-based vaccines against rotavirus and poliovirus.

  • Expression and immunoreactivity of HCV/HBV Epitopes
    World journal of gastroenterology, 2005
    Co-Authors: Xinyu Xiong, Xiao Liu, Yuan-ding Chen
    Abstract:

    AIM: To develop the epitope-based vaccines to prevent Hepatitis C virus (HCV) / Hepatitis B virus (HBV) infections. METHODS: The HCV core Epitopes C1 STNPKPQRKTKRNTNRRPQD (residuals aa2-21) and C2 VKFPGGGQIVGGVYLLPRR (residuals aa22-40), envelope epitope E GHRMAWDMMMNWSP (residuals aa315-328) and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC (residuals aa124-147) were displayed in five different sites of the flock house virus capsid protein as a vector, and expressed in E. coli cells (pET-3 system). Immunoreactivity of the Epitopes with anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B patients were determined. RESULTS: The expressed chimeric protein carrying the HCV Epitopes C1, C2, E (two times), L3C1-I2E-L1C2-L2E could react with anti-HCV antibodies. The expressed chimeric protein carrying the HBV Epitopes S, I3S could react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV Epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with anti-HCV and anti-HBs antibodies. CONCLUSION: These Epitopes have highly specific and sensitive immunoreaction and are useful in the development of epitope-based vaccines.

  • Immunoreactivity of HCV/HBV Epitopes displayed in an epitope-presenting system.
    Molecular immunology, 2005
    Co-Authors: Yuan-ding Chen, Xinyu Xiong, Xiao Liu, Yuling Wen, Yu-na Chen, Qing Dai, Zhiliang Cao
    Abstract:

    Abstract It has been demonstrated that the immunodominant region of the HCV core protein and the hepatitis B surface antigen (HBsAg) have high degree of reactivity. In order to construct a chimeric protein that carries HCV and HBV Epitopes and possesses immunogenicity to both HCV and HBV, four Epitopes derived from residues aa2–21 (epitope C1), aa22–40 (epitope C2) of the core protein, residues aa315–328 (epitope E) of E1 protein of HCV, and residues aa124–147 (epitope S) of HBsAg were chosen to be displayed in a conformation-specific manner on the outer surface of the Flock House virus capsid protein and expressed in E. coli cells. The reactivity of these Epitopes with antisera from hepatitis C and hepatitis B patients and induction of immune response in guinea pigs were determined. The results showed that when displayed in this system, the chimeric protein carrying only epitope S could react with anti-HBsAg positive human sera, elicit an anti-HBsAg response in guinea pigs. The chimeric protein carrying Epitopes C1, C2 and E could react with antibodies to different HCV genotypes, elicit an anti-HCV response in guinea pigs. The chimeric protein carrying Epitopes C1, C2, E, and S could react with antibodies against HCV and HBV, elicit anti-HCV and anti-HBsAg responses in guinea pigs. The results suggested that these Epitopes displayed in this form could be considered for development of epitope-based vaccines against HCV/HBV infections.

Alessandro Sette - One of the best experts on this subject based on the ideXlab platform.

  • The Use of the Immune Epitope Database to Study Autoimmune Epitope Data Related to Alopecia Areata.
    The journal of investigative dermatology. Symposium proceedings, 2015
    Co-Authors: Alessandro Sette, Sinu Paul, Kerrie Vaughan, Bjoern Peters
    Abstract:

    The Immune Epitope Database (IEDB) is a repository of published epitope data for infectious diseases, allergy, transplantation and autoimmunity. Herein we provide an introduction to the IEDB search interface, focusing on data related to autoimmune diseases, including alopecia areata (AA). We demonstrate how common questions related can be answered, such as how to search for specific autoantigens, epitope sequences, response types (B- and/or T-cell assays), or host, as well as how to search for Epitopes of known major histocompatibility complex restriction and for data related to a specific disease. Our survey of the data found that while as a whole Autoimmunity-specific records represent a significant portion (∼30%); Epitopes reported for AA are remarkably few, just 23 Epitopes from six antigens. This reveals a significant knowledge gap for AA, and suggests that additional mapping of Epitopes and identification of novel AA-associated autoantigens is warranted. Citing recently published examples, we show how bioinformatic, proteomic, and technological advances make it now increasingly feasible to identify Epitopes and novel antigens in human disease. The goal herein was to increase awareness of the IEDB as a free resource for the scientific community and to demonstrate its use in finding (existing) and analyzing (prediction) epitope data.

  • Applications for T-cell epitope queries and tools in the Immune Epitope Database and Analysis Resource
    Journal of Immunological Methods, 2010
    Co-Authors: Yohan Kim, Alessandro Sette, Bjoern Peters
    Abstract:

    The Immune Epitope Database and Analysis Resource (IEDB, http://www.iedb.org) hosts a continuously growing set of immune epitope data curated from the literature, as well as data submitted directly by experimental scientists. In addition, the IEDB hosts a collection of prediction tools for both MHC class I and II restricted T-cell Epitopes that are regularly updated. In this review, we provide an overview of T-cell epitope data and prediction tools provided by the IEDB. We then illustrate effective use of these resources to support experimental studies. We focus on two applications, namely identification of conserved Epitopes in novel strains of a previously studied pathogen, and prediction of novel T-cell Epitopes to facilitate vaccine design. We address common questions and concerns faced by users, and identify patterns of usage that have proven successful.

  • naive precursor frequencies and mhc binding rather than the degree of epitope diversity shape cd8 t cell immunodominance
    Journal of Immunology, 2008
    Co-Authors: Maya F Kotturi, Hilde Cheroutre, Howard M. Grey, Iain Scott, Michael J Buchmeier, Matthias Von Herrath, Tom Wolfe, John Sidney, Bjoern Peters, Alessandro Sette
    Abstract:

    The primary CD8 + T cell response of C57BL/6J mice against the 28 known Epitopes of lymphocytic choriomeningitis virus (LCMV) is associated with a clear immunodominance hierarchy whose mechanism has yet to be defined. To evaluate the role of epitope competition in immunodominance, we manipulated the number of CD8 + T cell Epitopes that could be recognized during LCMV infection. Decreasing epitope numbers, using a viral variant lacking dominant Epitopes or C57BL/6J mice lacking H-2K b , resulted in minor response increases for the remaining Epitopes and no new Epitopes being recognized. Increasing epitope numbers by using F 1 hybrid mice, delivery by recombinant vaccinia virus, or epitope delivery as a pool in IFA maintained the overall response pattern; however, changes in the hierarchy did become apparent. MHC binding affinity of these Epitopes was measured and was found to not strictly predict the hierarchy since in several cases similarly high binding affinities were associated with differences in immunodominance. In these instances the naive CD8 + T cell precursor frequency, directly measured by tetramer staining, correlated with the response hierarchy seen after LCMV infection. Finally, we investigated an escape mutant of the dominant GP33–41 epitope that elicited a weak response following LCMV variant virus infection. Strikingly, dominance loss likely reflects a substantial reduction in frequencies of naive precursors specific for this epitope. Thus, our results indicate that an intrinsic property of the epitope (MHC binding affinity) and an intrinsic property of the host (naive precursor frequency) jointly dictate the immunodominance hierarchy of CD8 + T cell responses.

  • Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines
    BMC bioinformatics, 2007
    Co-Authors: Huynh-hoa Bui, John Sidney, Nicholas Fusseder, Alessandro Sette
    Abstract:

    In an epitope-based vaccine setting, the use of conserved Epitopes would be expected to provide broader protection across multiple strains, or even species, than Epitopes derived from highly variable genome regions. Conversely, in a diagnostic and disease monitoring setting, Epitopes that are specific to a given pathogen strain, for example, can be used to monitor responses to that particular infectious strain. In both cases, concrete information pertaining to the degree of conservancy of the epitope(s) considered is crucial. To assist in the selection of Epitopes with the desired degree of conservation, we have developed a new tool to determine the variability of Epitopes within a given set of protein sequences. The tool was implemented as a component of the Immune Epitope Database and Analysis Resources (IEDB), and is directly accessible at http://tools.immuneepitope.org/tools/conservancy . An epitope conservancy analysis tool was developed to analyze the variability or conservation of Epitopes. The tool is user friendly, and is expected to aid in the design of epitope-based vaccines and diagnostics.

  • ab and t cell Epitopes of influenza a virus knowledge and opportunities
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Huynh-hoa Bui, Bjoern Peters, Erika Assarsson, Innocent N Mbawuike, Alessandro Sette
    Abstract:

    The Immune Epitope Database and Analysis Resources (IEDB) (www.immuneepitope.org) was recently developed to capture epitope related data. IEDB also hosts various bioinformatics tools that can be used to identify novel Epitopes as well as to analyze and visualize existing epitope data. Herein, a comprehensive analysis was undertaken (i) to compile and inventory existing knowledge regarding influenza A Epitopes and (ii) to determine possible cross-reactivities of identified Epitopes among avian H5N1 and human influenza strains. At present, IEDB contains >600 different Epitopes derived from 58 different strains and 10 influenza A proteins. By using the IEDB analysis resources, conservancy analyses were performed, and several conserved and possibly cross-reactive Epitopes were identified. Significant gaps in the current knowledge were also revealed, including paucity of Ab Epitopes in comparison with T cell Epitopes, limited number of Epitopes reported for avian influenza strains/subtypes, and limited number of Epitopes reported from proteins other than hemagglutinin and nucleoprotein. This analysis provides a resource for researchers to access existing influenza epitope data. At the same time, the analysis illustrates gaps in our collective knowledge that should inspire directions for further study of immunity against the influenza A virus.