CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection
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{"title"=>"CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection", "type"=>"journal", "authors"=>[{"first_name"=>"Sama", "last_name"=>"Adnan", "scopus_author_id"=>"15069201400"}, {"first_name"=>"Arnaud D.", "last_name"=>"Colantonio", "scopus_author_id"=>"23099294600"}, {"first_name"=>"Yi", "last_name"=>"Yu", "scopus_author_id"=>"55574215231"}, {"first_name"=>"Jacqueline", "last_name"=>"Gillis", "scopus_author_id"=>"7101981459"}, {"first_name"=>"Fay E.", "last_name"=>"Wong", "scopus_author_id"=>"9735225100"}, {"first_name"=>"Ericka A.", "last_name"=>"Becker", "scopus_author_id"=>"16244219500"}, {"first_name"=>"Michael", "last_name"=>"Piatak", "scopus_author_id"=>"7003985150"}, {"first_name"=>"R. Keith", "last_name"=>"Reeves", "scopus_author_id"=>"18435214400"}, {"first_name"=>"Jeffrey D.", "last_name"=>"Lifson", "scopus_author_id"=>"7006391588"}, {"first_name"=>"Shelby L.", "last_name"=>"O’Connor", "scopus_author_id"=>"56543615500"}, {"first_name"=>"R. Paul", "last_name"=>"Johnson", "scopus_author_id"=>"35227436000"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"25688559", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "doi"=>"10.1371/journal.ppat.1004633", "issn"=>"15537374", "scopus"=>"2-s2.0-84924389991", "pui"=>"602902085", "sgr"=>"84924389991"}, "id"=>"64cbb979-4570-3154-9c53-10fbc4b520a3", "abstract"=>"The live attenuated simian immunodeficiency virus (LASIV) vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective efficacy. Here, we exploit deep sequencing technology and comprehensive CD8 T cell epitope mapping to deconstruct the CD8 T cell response, to identify the regions of immune pressure and viral escape, and to delineate the effect of epitope escape on the evolution of the CD8 T cell response in SIVΔnef-vaccinated animals. We demonstrate that the initial CD8 T cell response in the acute phase of SIVΔnef infection is mounted predominantly against more variable epitopes, followed by widespread sequence evolution and viral escape. Furthermore, we show that epitope escape expands the CD8 T cell repertoire that targets highly conserved epitopes, defined as anentropic specificity, and generates de novo responses to the escaped epitope variants during the vaccination period. These results correlate SIVΔnef-induced protection with expanded anentropic specificity and increased response depth. Importantly, these findings render SIVΔnef, long the gold standard in HIV/SIV vaccine research, as a proof-of-concept vaccine that highlights the significance of the twin principles of anentropic specificity and repertoire depth in successful vaccine design.", "link"=>"http://www.mendeley.com/research/cd8-t-cell-response-maturation-defined-anentropic-specificity-repertoire-depth-correlates-siv%CE%B4nefind", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>2}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1909530"], "description"=>"<p>Major alleles expressed as determined by MHC I genotyping.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311456, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.t001", "stats"=>{"downloads"=>4, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Major_alleles_expressed_as_determined_by_MHC_I_genotyping_/1311456", "title"=>"Major alleles expressed as determined by MHC I genotyping.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909528"], "description"=>"<p>(A) No change in breadth of the CD8 T cell response was observed as measured by the number epitope-specific CD8 T cell responses per animal at weeks 5 and 20. (B) The cumulative breadth at week 20 was significantly higher than the breadth at Week 5 (p = 0.0036). The cumulative breadth at week 20 included all the week 5 epitope responses, even if they were not detected at week 20. (C) Phenotypic analysis of SL8 tetramer+ CD8 T cells from peripheral blood. SL8-specific CD8 T cells exhibited a central memory profile at week 20, as demonstrated by increased expression of CD28 (p = 0.0087), CCR7 (p = 0.0006) and CD127 (p<0.0001) markers and a decrease in perforin (p<0.0001) and Ki67 (p = 0.0194). (D) Tat SL8 epitope heat maps showing 82% and 94% percent variation at week 4 for animals 201–02 and 206–00, respectively. Below, two graphs show the primary and recall SL8-specific CD8 T cell responses (squares) as measured by Mamu-A*01-SL8 tetramer staining (left) and IFN-γ ELISPOT (right) in the context of plasma viral loads of SIVΔnef (triangles) and SIVmac251 challenge virus (circles) in 201–02 (dark blue) and 206–00 (green).</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311454, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g008", "stats"=>{"downloads"=>0, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Escaped_responses_contribute_to_the_cumulative_breadth_of_the_CD8_T_cell_repertoire_/1311454", "title"=>"Escaped responses contribute to the cumulative breadth of the CD8 T cell repertoire.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909525"], "description"=>"<p>(A) In animal 225–97, 7 of the 9 highest frequency nonsynonymous mutations at week 20 were within mapped CD8 T cell epitopes. (B) Epitope-specific CD8 T cell responses declined as their epitopes escaped. Time of 50% escape is shown between parentheses. (C) The sequence evolution of 4 CD8 T cell epitopes mapped from animal 225–97 demonstrates the dynamic nature of viral escape. In all cases, escape variants were over taken by other variants at a later time point.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311451, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g005", "stats"=>{"downloads"=>1, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sequence_evolution_and_CD8_T_cell_responses_overlap_positionally_and_temporally_/1311451", "title"=>"Sequence evolution and CD8 T cell responses overlap, positionally and temporally.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909524"], "description"=>"<p>The entropy of a 9 amino-acid window is graphed at each amino acid position. The entropy of each amino acid was calculated by aligning 10 SIVsmm proteomes.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311450, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g004", "stats"=>{"downloads"=>1, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_entropy_of_SIVsmm_proteins_varies_widely_/1311450", "title"=>"The entropy of SIVsmm proteins varies widely.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909519"], "description"=>"<p>(A) Of the 37 CD8 T cell epitopes mapped for 6 SIVΔnef-vaccinated animals at week 5, only 14 epitopes were recognized at week 20. Approximately two thirds of the epitopes recognized at week 20 were novel responses not previously detected. (B) The entropy of the immunodominant epitope decreased significantly between weeks 5 and 20 (p = .039).</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311445, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g003", "stats"=>{"downloads"=>1, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epitope_mapping_reveals_a_change_in_the_CD8_T_cell_repertoire_and_in_immunodominance_/1311445", "title"=>"Epitope mapping reveals a change in the CD8 T cell repertoire and in immunodominance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909518"], "description"=>"<p>(A) The total magnitude of the PBMC CD8 T cell response as measured by IFN-γ ELISPOT assays using whole protein overlapping peptide pools. (B) The breadth of the PBMC CD8 T cell response as measured by the average number of positive pools at weeks 5 and 20. (C) The magnitude and the breadth of lymph node CD8 T cell responses. The total magnitude of lymph node CD8 T cell response to SIV was determined by adding the responses for all 30 peptide pools spanning the entire SIVΔnef proteome. (D) The Gag and Pol-specific CD8 T cell response as a fraction of the total SIV-specific CD8 T cell response increased significantly between weeks 5 and 16/20 (p<0.0001), plateauing at week 16.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311444, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g002", "stats"=>{"downloads"=>1, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_of_the_epitope_specificity_of_SIV_specific_CD8_T_cell_responses_in_SIV_916_nef_vaccinated_animals_/1311444", "title"=>"Evolution of the epitope specificity of SIV-specific CD8 T cell responses in SIVΔnef-vaccinated animals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909527"], "description"=>"<p>The response conservation index, a measure of the CD8 T cell response weighted negatively for entropy, increases for every animal between weeks 5 and 20 (p = 0.0156). The response conservation index for an animal at a given time point is calculated as<math><mrow><mo>∑</mo><mrow><mi>i</mi><mo>=</mo><mn>0</mn></mrow><mi>n</mi><mrow><msub><mi>F</mi><mi>i</mi></msub></mrow><mo stretchy=\"false\">(</mo><mn>1</mn><mo>−</mo><msub><mi>E</mi><mi>i</mi></msub><mo stretchy=\"false\">)</mo></mrow></math>, where F is the frequency of each epitope-specific CD8 T cell response as a fraction of the total magnitude of the response, E is the entropy of the epitope, and n is the number of epitope-specific CD8 T cell responses.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311453, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g007", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_anentropic_specificity_of_SIV_specific_CD8_T_cell_responses_between_weeks_5_and_20_after_SIV_916_nef_vaccination_/1311453", "title"=>"Increased anentropic specificity of SIV-specific CD8 T cell responses between weeks 5 and 20 after SIVΔnef vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909526"], "description"=>"<p>(A) The four immunodominant epitopes from all animals were plotted according to their entropies and whether they escaped the CD8 T cell response. Anentropic epitopes demonstrated significantly less escape than highly entropic epitopes. Anentropic epitopes were predominantly from Gag and Pol. (B) While CD8 T cell responses targeting conserved epitopes were maintained over time, responses specific to variable epitopes declined in magnitude.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311452, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g006", "stats"=>{"downloads"=>3, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_As_entropic_epitopes_escape_the_CD8_T_cell_responses_specific_for_these_epitopes_wane_/1311452", "title"=>"As entropic epitopes escape, the CD8 T cell responses specific for these epitopes wane.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909531", "https://ndownloader.figshare.com/files/1909532", "https://ndownloader.figshare.com/files/1909533", "https://ndownloader.figshare.com/files/1909534", "https://ndownloader.figshare.com/files/1909535"], "description"=>"<div><p>The live attenuated simian immunodeficiency virus (LASIV) vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective efficacy. Here, we exploit deep sequencing technology and comprehensive CD8 T cell epitope mapping to deconstruct the CD8 T cell response, to identify the regions of immune pressure and viral escape, and to delineate the effect of epitope escape on the evolution of the CD8 T cell response in SIVΔnef-vaccinated animals. We demonstrate that the initial CD8 T cell response in the acute phase of SIVΔnef infection is mounted predominantly against more variable epitopes, followed by widespread sequence evolution and viral escape. Furthermore, we show that epitope escape expands the CD8 T cell repertoire that targets highly conserved epitopes, defined as anentropic specificity, and generates de novo responses to the escaped epitope variants during the vaccination period. These results correlate SIVΔnef-induced protection with expanded anentropic specificity and increased response depth. Importantly, these findings render SIVΔnef, long the gold standard in HIV/SIV vaccine research, as a proof-of-concept vaccine that highlights the significance of the twin principles of anentropic specificity and repertoire depth in successful vaccine design.</p></div>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311457, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004633.s001", "https://dx.doi.org/10.1371/journal.ppat.1004633.s002", "https://dx.doi.org/10.1371/journal.ppat.1004633.s003", "https://dx.doi.org/10.1371/journal.ppat.1004633.s004", "https://dx.doi.org/10.1371/journal.ppat.1004633.s005"], "stats"=>{"downloads"=>5, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD8_T_Cell_Response_Maturation_Defined_by_Anentropic_Specificity_and_Repertoire_Depth_Correlates_with_SIV_916_nef_induced_Protection_/1311457", "title"=>"CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909516"], "description"=>"<p>(A) Plasma viral loads (RNA copies/ml) of 12 SIVΔnef-infected animals. The dashed black line marks the 30 copies/ml threshold. (B) Frequency of nonsynonymous mutations (>10% variant frequency) increased significantly (p = 0.001) between weeks 4 and 20 for the 5 animals whose virus was sequenced at both time points. Squares are colored according to variant frequency: blue: 10–15%, green: 16–30%, orange: 31–50%, red: 51–80%, and dark red: 81–100%. (C) The sequence evolution in animal 225–97 at weeks 2, 4 and 20 is displayed for every amino acid in the SIVΔnef proteome. The top left corner is the first amino acid of Gag and the bottom right corner is the last expressed amino acid of the truncated Nef. (D) Extensive SIVΔnef sequence evolution in animals 290–07 and 292–07 at week 20, despite undetectable plasma viral load. Lymph node cell-associated viral RNA was isolated for sequencing. (E) Significant increase (p = 0.031) in the number of nonsynonymous mutations between weeks 4 and 20 for 5 animals whose virus was sequenced at both time points.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311442, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g001", "stats"=>{"downloads"=>5, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extensive_sequence_evolution_in_SIV_916_nef_/1311442", "title"=>"Extensive sequence evolution in SIVΔnef.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1909529"], "description"=>"<p>(A) FW9, an epitope mapped in animal 256–00, escaped the CD8 T cell response by mutating a histidine into a tyrosine (H831Y). The escape mutant was recognized at week 38 but not at week 5, when the original epitope was mapped. (B) The GY9 epitope was recognized at week 5 in animal 256–00 as well as week 38, while its escape variant K76R was recognized only at week 38. The third escape variant S77G was not recognized at either time point.</p>", "links"=>[], "tags"=>["siv", "Repertoire Depth Correlates", "CD 8 T cell response", "LASIV", "hiv", "anentropic specificity", "CD 8 T Cell Response Maturation Defined", "CD 8 T cell epitope mapping", "CD 8 T cell repertoire", "vaccine"], "article_id"=>1311455, "categories"=>["Biological Sciences"], "users"=>["Sama Adnan", "Arnaud D. Colantonio", "Yi Yu", "Jacqueline Gillis", "Fay E. Wong", "Ericka A. Becker", "Michael Piatak Jr", "R. Keith Reeves", "Jeffrey D. Lifson", "Shelby L. O’Connor", "R. Paul Johnson"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004633.g009", "stats"=>{"downloads"=>4, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_CD8_T_cell_repertoire_depth_during_SIV_916_nef_vaccination_/1311455", "title"=>"Increased CD8 T cell repertoire depth during SIVΔnef vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-17 04:00:25"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
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  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"29", "full-text"=>"26", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"16", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"29", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"18", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
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  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"4", "cited-by"=>"1", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"28", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"45", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"152", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"19", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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