The Experts below are selected from a list of 124746 Experts worldwide ranked by ideXlab platform
Richard A Koup - One of the best experts on this subject based on the ideXlab platform.
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a novel approach to the analysis of specificity clonality and frequency of hiv specific t cell responses reveals a potential mechanism for control of viral escape
Journal of Immunology, 2002Co-Authors: Daniel C Douek, Michael R Betts, Jason M Brenchley, Brenna J Hill, David R Ambrozak, Kaleung Ngai, Nitin J Karandikar, Joseph P Casazza, Richard A KoupAbstract:Escape from the CD8 + T cell response through Epitope mutations can lead to loss of immune control of HIV replication. Theoretically, escape from CD8 + T cell recognition is less likely when multiple TCRs target individual MHC/peptide complexes, thereby increasing the chance that amino acid changes in the Epitope could be tolerated. We studied the CD8 + T cell response to six immunodominant Epitopes in five HIV-infected subjects using a novel approach combining peptide stimulation, cell surface cytokine capture, flow cytometric sorting, anchored RT-PCR, and real-time quantitative clonotypic TCR tracking. We found marked variability in the number of clonotypes targeting individual Epitopes. One subject recognized a single Epitope with six clonotypes, most of which were able to recognize and lyse cells expressing a major Epitope variant that arose. Additionally, multiple clonotypes remained expanded during the course of infection, irrespective of Epitope variant frequency. Thus, CD8 + T cells comprising multiple TCR clonotypes may expand in vivo in response to individual Epitopes, and may increase the ability of the response to recognize virus escape mutants.
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putative immunodominant human immunodeficiency virus specific cd8 t cell responses cannot be predicted by major histocompatibility complex class i haplotype
Journal of Virology, 2000Co-Authors: Michael R Betts, Joseph P Casazza, Brent A Patterson, Shar L Waldrop, Wendy L Trigona, Florian Kern, Louis J Picker, Richard A KoupAbstract:Recent studies of human immunodeficiency virus (HIV)-specific CD8(+) T cells have focused on responses to single, usually HLA-A2-restricted Epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one Epitope is representative of the total response is unconfirmed. Here we assess Epitope immunodominance and HIV-specific CD8(+) T-cell response complexity using cytokine flow cytometry to examine CD8(+) T-cell responses in 11 HLA-A2(+) HIV(+) individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 Epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8(+) T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV Epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted Epitopes were recognized, but CD8(+) T-cell responses were detected to Epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8(+) T-cell response to HIV is not adequately represented by the response to a single Epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8(+) T-cell responses will require assessment of the response to all possible Epitopes.
Salvador Eugenio C Caoili - One of the best experts on this subject based on the ideXlab platform.
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expressing redundancy among linear Epitope sequence data based on residue level physicochemical similarity in the context of antigenic cross reaction
Advances in Bioinformatics, 2016Co-Authors: Salvador Eugenio C CaoiliAbstract:Epitope-based design of vaccines, immunotherapeutics, and immunodiagnostics is complicated by structural changes that radically alter immunological outcomes. This is obscured by expressing redundancy among linear-Epitope data as fractional sequence-alignment identity, which fails to account for potentially drastic loss of binding affinity due to single-residue substitutions even where these might be considered conservative in the context of classical sequence analysis. From the perspective of immune function based on molecular recognition of Epitopes, functional redundancy of Epitope data (FRED) thus may be defined in a biologically more meaningful way based on residue-level physicochemical similarity in the context of antigenic cross-reaction, with functional similarity between Epitopes expressed as the Shannon information entropy for differential Epitope binding. Such similarity may be estimated in terms of structural differences between an immunogen Epitope and an antigen Epitope with reference to an idealized binding site of high complementarity to the immunogen Epitope, by analogy between protein folding and ligand-receptor binding; but this underestimates potential for cross-reactivity, suggesting that Epitope-binding site complementarity is typically suboptimal as regards immunologic specificity. The apparently suboptimal complementarity may reflect a tradeoff to attain optimal immune function that favors generation of immune-system components each having potential for cross-reactivity with a variety of Epitopes.
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expressing redundancy among linear Epitope sequence data based on residue level physicochemical similarity in the context of antigenic cross reaction
Advances in Bioinformatics, 2016Co-Authors: Salvador Eugenio C CaoiliAbstract:Epitope-based design of vaccines, immunotherapeutics, and immunodiagnostics is complicated by structural changes that radically alter immunological outcomes. This is obscured by expressing redundancy among linear-Epitope data as fractional sequence-alignment identity, which fails to account for potentially drastic loss of binding affinity due to single-residue substitutions even where these might be considered conservative in the context of classical sequence analysis. From the perspective of immune function based on molecular recognition of Epitopes, functional redundancy of Epitope data (FRED) thus may be defined in a biologically more meaningful way based on residue-level physicochemical similarity in the context of antigenic cross-reaction, with functional similarity between Epitopes expressed as the Shannon information entropy for differential Epitope binding. Such similarity may be estimated in terms of structural differences between an immunogen Epitope and an antigen Epitope with reference to an idealized binding site of high complementarity to the immunogen Epitope, by analogy between protein folding and ligand-receptor binding; but this underestimates potential for cross-reactivity, suggesting that Epitope-binding site complementarity is typically suboptimal as regards immunologic specificity. The apparently suboptimal complementarity may reflect a tradeoff to attain optimal immune function that favors generation of immune-system components each having potential for cross-reactivity with a variety of Epitopes.
Juergen Hammer - One of the best experts on this subject based on the ideXlab platform.
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identification of novel immunodominant cd4 th1 type t cell peptide Epitopes from herpes simplex virus glycoprotein d that confer protective immunity
Journal of Virology, 2003Co-Authors: Lbachir Benmohamed, Juergen Hammer, Georges Bertrand, Cory D Mcnamara, Helene Grasmasse, Steven L Wechsler, Anthony B NesburnAbstract:The molecular characterization of the Epitope repertoire on herpes simplex virus (HSV) antigens would greatly expand our knowledge of HSV immunity and improve immune interventions against herpesvirus infections. HSV glycoprotein D (gD) is an immunodominant viral coat protein and is considered an excellent vaccine candidate antigen. By using the TEpitope prediction algorithm, we have identified and characterized a total of 12 regions within the HSV type 1 (HSV-1) gD bearing potential CD4(+) T-cell Epitopes, each 27 to 34 amino acids in length. Immunogenicity studies of the corresponding medium-sized peptides confirmed all previously known gD Epitopes and additionally revealed four new immunodominant regions (gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), each containing naturally processed Epitopes. These Epitopes elicited potent T-cell responses in mice of diverse major histocompatibility complex backgrounds. Each of the four new immunodominant peptide Epitopes generated strong CD4(+) Th1 T cells that were biologically active against HSV-1-infected bone marrow-derived dendritic cells. Importantly, immunization of H-2(d) mice with the four newly identified CD4(+) Th1 peptide Epitopes but not with four CD4(+) Th2 peptide Epitopes induced a robust protective immunity against lethal ocular HSV-1 challenge. These peptide Epitopes may prove to be important components of an effective immunoprophylactic strategy against herpes.
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melanoma cells present a mage 3 Epitope to cd4 cytotoxic t cells in association with histocompatibility leukocyte antigen dr11
Journal of Experimental Medicine, 1999Co-Authors: Simona Manici, Francesco Sinigaglia, Tiziana Sturniolo, Maria Adele Imro, Juergen Hammer, Christoph Noppen, Giulio C Spagnoli, Benedetta Mazzi, Matteo Bellone, Paolo DellabonaAbstract:In this study we used TEpitope, a new Epitope prediction software, to identify sequence segments on the MAGE-3 protein with promiscuous binding to histocompatibility leukocyte antigen (HLA)-DR molecules. Synthetic peptides corresponding to the identified sequences were synthesized and used to propagate CD4+ T cells from the blood of a healthy donor. CD4+ T cells strongly recognized MAGE-3281–295 and, to a lesser extent, MAGE-3141–155 and MAGE-3146–160. Moreover, CD4+ T cells proliferated in the presence of recombinant MAGE-3 after processing and presentation by autologous antigen presenting cells, demonstrating that the MAGE-3 Epitopes recognized are naturally processed. CD4+ T cells, mostly of the T helper 1 type, showed specific lytic activity against HLA-DR11/MAGE-3–positive melanoma cells. Cold target inhibition experiments demonstrated indeed that the CD4+ T cells recognized MAGE-3281–295 in association with HLA-DR11 on melanoma cells. This is the first evidence that a tumor-specific shared antigen forms CD4+ T cell Epitopes. Furthermore, we validated the use of algorithms for the prediction of promiscuous CD4+ T cell Epitopes, thus opening the possibility of wide application to other tumor-associated antigens. These results have direct implications for cancer immunotherapy in the design of peptide-based vaccines with tumor-specific CD4+ T cell Epitopes.
Thenmalarchelvi Rathinavelan - One of the best experts on this subject based on the ideXlab platform.
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DataSheet_15_Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach.xlsx
'Frontiers Media SA', 2021Co-Authors: Patil Pranita Uttamrao, Chakkarai Sathyaseelan, Ponoop Prasad L. Patro, Thenmalarchelvi RathinavelanAbstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising Epitopes. Among them, ORF9b B-cell and T-cell Epitopes are the most promising followed by M.ext and ORF3c Epitopes. ORF9b40-48 (CD8+ T-cell Epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell Epitopes. Structure-based B-cell Epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell Epitopes (ORF9b65-69). ORF3c CD4+ T-cell Epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell Epitope (ORF3c14-22) have also been identified as the candidate Epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext Epitopes are finally shortlisted as potent Epitopes. Mutation analysis has further revealed that the shortlisted potent uORF Epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) Epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell Epitopes identified here along with canonical ORF Epitopes may aid in the design of a promising Epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.
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DataSheet_14_Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach.xlsx
'Frontiers Media SA', 2021Co-Authors: Patil Pranita Uttamrao, Chakkarai Sathyaseelan, Ponoop Prasad L. Patro, Thenmalarchelvi RathinavelanAbstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising Epitopes. Among them, ORF9b B-cell and T-cell Epitopes are the most promising followed by M.ext and ORF3c Epitopes. ORF9b40-48 (CD8+ T-cell Epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell Epitopes. Structure-based B-cell Epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell Epitopes (ORF9b65-69). ORF3c CD4+ T-cell Epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell Epitope (ORF3c14-22) have also been identified as the candidate Epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext Epitopes are finally shortlisted as potent Epitopes. Mutation analysis has further revealed that the shortlisted potent uORF Epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) Epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell Epitopes identified here along with canonical ORF Epitopes may aid in the design of a promising Epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.
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Table_1_Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach.docx
'Frontiers Media SA', 2021Co-Authors: Patil Pranita Uttamrao, Chakkarai Sathyaseelan, Ponoop Prasad L. Patro, Thenmalarchelvi RathinavelanAbstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising Epitopes. Among them, ORF9b B-cell and T-cell Epitopes are the most promising followed by M.ext and ORF3c Epitopes. ORF9b40-48 (CD8+ T-cell Epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell Epitopes. Structure-based B-cell Epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell Epitopes (ORF9b65-69). ORF3c CD4+ T-cell Epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell Epitope (ORF3c14-22) have also been identified as the candidate Epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext Epitopes are finally shortlisted as potent Epitopes. Mutation analysis has further revealed that the shortlisted potent uORF Epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) Epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell Epitopes identified here along with canonical ORF Epitopes may aid in the design of a promising Epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.
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DataSheet_13_Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach.xlsx
'Frontiers Media SA', 2021Co-Authors: Patil Pranita Uttamrao, Chakkarai Sathyaseelan, Ponoop Prasad L. Patro, Thenmalarchelvi RathinavelanAbstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising Epitopes. Among them, ORF9b B-cell and T-cell Epitopes are the most promising followed by M.ext and ORF3c Epitopes. ORF9b40-48 (CD8+ T-cell Epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell Epitopes. Structure-based B-cell Epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell Epitopes (ORF9b65-69). ORF3c CD4+ T-cell Epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell Epitope (ORF3c14-22) have also been identified as the candidate Epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext Epitopes are finally shortlisted as potent Epitopes. Mutation analysis has further revealed that the shortlisted potent uORF Epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) Epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell Epitopes identified here along with canonical ORF Epitopes may aid in the design of a promising Epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.
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DataSheet_10_Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach.xlsx
'Frontiers Media SA', 2021Co-Authors: Patil Pranita Uttamrao, Chakkarai Sathyaseelan, Ponoop Prasad L. Patro, Thenmalarchelvi RathinavelanAbstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising Epitopes. Among them, ORF9b B-cell and T-cell Epitopes are the most promising followed by M.ext and ORF3c Epitopes. ORF9b40-48 (CD8+ T-cell Epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell Epitopes. Structure-based B-cell Epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell Epitopes (ORF9b65-69). ORF3c CD4+ T-cell Epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell Epitope (ORF3c14-22) have also been identified as the candidate Epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext Epitopes are finally shortlisted as potent Epitopes. Mutation analysis has further revealed that the shortlisted potent uORF Epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) Epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell Epitopes identified here along with canonical ORF Epitopes may aid in the design of a promising Epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.
Michael R Betts - One of the best experts on this subject based on the ideXlab platform.
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a novel approach to the analysis of specificity clonality and frequency of hiv specific t cell responses reveals a potential mechanism for control of viral escape
Journal of Immunology, 2002Co-Authors: Daniel C Douek, Michael R Betts, Jason M Brenchley, Brenna J Hill, David R Ambrozak, Kaleung Ngai, Nitin J Karandikar, Joseph P Casazza, Richard A KoupAbstract:Escape from the CD8 + T cell response through Epitope mutations can lead to loss of immune control of HIV replication. Theoretically, escape from CD8 + T cell recognition is less likely when multiple TCRs target individual MHC/peptide complexes, thereby increasing the chance that amino acid changes in the Epitope could be tolerated. We studied the CD8 + T cell response to six immunodominant Epitopes in five HIV-infected subjects using a novel approach combining peptide stimulation, cell surface cytokine capture, flow cytometric sorting, anchored RT-PCR, and real-time quantitative clonotypic TCR tracking. We found marked variability in the number of clonotypes targeting individual Epitopes. One subject recognized a single Epitope with six clonotypes, most of which were able to recognize and lyse cells expressing a major Epitope variant that arose. Additionally, multiple clonotypes remained expanded during the course of infection, irrespective of Epitope variant frequency. Thus, CD8 + T cells comprising multiple TCR clonotypes may expand in vivo in response to individual Epitopes, and may increase the ability of the response to recognize virus escape mutants.
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putative immunodominant human immunodeficiency virus specific cd8 t cell responses cannot be predicted by major histocompatibility complex class i haplotype
Journal of Virology, 2000Co-Authors: Michael R Betts, Joseph P Casazza, Brent A Patterson, Shar L Waldrop, Wendy L Trigona, Florian Kern, Louis J Picker, Richard A KoupAbstract:Recent studies of human immunodeficiency virus (HIV)-specific CD8(+) T cells have focused on responses to single, usually HLA-A2-restricted Epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one Epitope is representative of the total response is unconfirmed. Here we assess Epitope immunodominance and HIV-specific CD8(+) T-cell response complexity using cytokine flow cytometry to examine CD8(+) T-cell responses in 11 HLA-A2(+) HIV(+) individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 Epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8(+) T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV Epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted Epitopes were recognized, but CD8(+) T-cell responses were detected to Epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8(+) T-cell response to HIV is not adequately represented by the response to a single Epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8(+) T-cell responses will require assessment of the response to all possible Epitopes.