Search CTL/CD8+ T-Cell Epitope Database

Found 8 matching records:

Displaying record number 62125

HXB2 Location	Gag(147-155) p24(15-23)	Gag Epitope Map
Author Location	p24(15-23)
Epitope	`ISPRTLNAW`	Epitope Alignment
Epitope Name	B*57-IW9
Species (MHC/HLA)	human(B*57)
Immunogen	computer prediction
Country	Argentina
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
IW9 is the representative protective-HLA-B*57-restricted epitope of a controller. It is highly networked. IW9 binds HLA-B*5701 and B63, and has a normalized network score of 9.17.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Gaiha2019 Gaurav D. Gaiha, Elizabeth J. Rossin, Jonathan Urbach, Christian Landeros, David R. Collins, Chioma Nwonu, Itai Muzhingi, Melis N. Anahtar, Olivia M. Waring, Alicja Piechocka-Trocha, Michael Waring, Daniel P. Worrall, Musie S. Ghebremichael, Ruchi M. Newman, Karen A. Power, Todd M. Allen, James Chodosh, and Bruce D. Walker. Structural Topology Defines Protective CD8+ T Cell Epitopes in the HIV Proteome. Science, 364(6439):480-484, 3 May 2019. PubMed ID: 31048489. Show all entries for this paper.

Displaying record number 62010

HXB2 Location	Gag(162-172) p24(30-40)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	B*57-KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
Protective epitope, B*57-KF11 contains highly networked residues that bridge the N- and C- terminal domains of Gag p24 and that contact HLA anchor and TCR sites. While A31 and F40 are HLA anchor residues, the rest of the residues - F32, S33, P34, E35, V36, I37, P38, M39 - contact TCR. It has a normalized network score of 8.78 and is presented by B*5701, B*5703 or B63.
Supplementary Table S3 contains 260 Epitope Network Scores of HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62126

HXB2 Location	Vif(31-39)	Vif Epitope Map
Author Location	Vif(31-39)
Epitope	`ISKKAKGWF`	Epitope Alignment
Epitope Name	B*57-IF9
Species (MHC/HLA)	human(B*57)
Immunogen	computer prediction
Country	Argentina
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
IF9 is the representative protective-HLA-B*57-restricted epitope of a progressor. It is poorly networked. IF9 binds HLA-B*5701, and has a normalized network score of 1.84.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62122

HXB2 Location	gp160(78-86) gp120(78-86)	gp160 Epitope Map
Author Location	gp120(78-86)
Epitope	`DPNPQEVVL`	Epitope Alignment
Epitope Name	B*35-DL9
Species (MHC/HLA)	human(B*3501)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
Risk epitope, B*35-DL9 contains poorly networked residues that rarely contact HLA anchor and TCR sites. While P79 and L86 are HLA anchor residues, the rest of the residues - N80, P81, Q82, E83, V84, V85 - do not contact TCR well. DL9 has a normalized network score of 1.95 and is presented by B*3501.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62123

HXB2 Location	gp160(121-129) gp120(121-129)	gp160 Epitope Map
Author Location	gp120(121-129)
Epitope	`KLTPLCVTL`	Epitope Alignment
Epitope Name	A*02-KL9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
KL9 is the representative neutral HLA-A*02-restricted immunodominant epitope of a controller. It contains highly networked residues from the V1V2 stem of gp120. High epitope network scores distinguished controllers from progressors. Residues L122 and L129 are HLA anchors while T123, L125 and C126 are TCR contacts. In models this epitope is seen more clearly in the open configuration of gp120 trimers. KL9 binds HLA-A*0201, and has a normalized network score of 7.99.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62124

HXB2 Location	gp160(298-307) gp120(298-307)	gp160 Epitope Map
Author Location	gp120(298-307)
Epitope	`RPNNNTRKSI`	Epitope Alignment
		Show epitope variants
Epitope Name	B*07-RI10
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
RI10 is the representative neutral HLA-B*07-restricted immunodominant epitope of a progressor. It contains low network score residues from V3 in both open or closed configurations of trimeric gp120. P299 is an HLA anchor and R304 is the only mild TCR contact. RI10 binds HLA-A*0702, and has a normalized network score of 3.39.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62128

HXB2 Location	Nef(90-97)	Nef Epitope Map
Author Location	Nef(90-97)
Epitope	`FLKEKGGL`	Epitope Alignment
Epitope Name	B*08-FL8
Species (MHC/HLA)	human(B*08)
Immunogen	computer prediction
Country	Argentina
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
FL8 is the representative epitope of a low network score with a robust proliferative CTL response. FL8 binds HLA-B*0801, and has a normalized network score of 1.75. Numerous mutations were detected in this epitope (as opposed to similar high network scoring epitopes), which abrogated later CTL recognition. K92 and K94 were HLA anchors while L91, E93, G95 and G96 make TCR contacts.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Displaying record number 62127

HXB2 Location	Nef(135-143)	Nef Epitope Map
Author Location	Nef(135-143)
Epitope	`YPLTFGWCF`	Epitope Alignment
Epitope Name	B*53-YF9
Species (MHC/HLA)	human(B*53)
Immunogen	computer prediction
Country	Argentina
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
YF9 is the representative epitope of a high network score with a robust proliferative CTL response. YF9 binds HLA-B*5301 or B*1801, and has a normalized network score of 7.2. No sequence variations were detected in this epitope (as opposed to similar low network scoring epitopes). P136 and F143 were HLA anchors while L137, G140, W141 and C142 make TCR contacts.
Supplementary Table S3 contains Epitope Network Scores of 260 HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.