CD8+ T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes
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{"title"=>"CD8+ T-cell responses to Trypanosoma cruzi are highly focused on strain-variant trans-sialidase epitopes", "type"=>"journal", "authors"=>[{"first_name"=>"Diana L.", "last_name"=>"Martin", "scopus_author_id"=>"7406285982"}, {"first_name"=>"D. Brent", "last_name"=>"Weatherly", "scopus_author_id"=>"8619100600"}, {"first_name"=>"Susana A.", "last_name"=>"Laucella", "scopus_author_id"=>"6602835334"}, {"first_name"=>"Melissa A.", "last_name"=>"Cabinian", "scopus_author_id"=>"14321156900"}, {"first_name"=>"Matthew T.", "last_name"=>"Crim", "scopus_author_id"=>"36980543700"}, {"first_name"=>"Susan", "last_name"=>"Sullivan", "scopus_author_id"=>"15054932300"}, {"first_name"=>"Mark", "last_name"=>"Heiges", "scopus_author_id"=>"12778059400"}, {"first_name"=>"Sarah H.", "last_name"=>"Craven", "scopus_author_id"=>"14321212900"}, {"first_name"=>"Charles S.", "last_name"=>"Rosenberg", "scopus_author_id"=>"14322514700"}, {"first_name"=>"Matthew H.", "last_name"=>"Collins", "scopus_author_id"=>"10140443800"}, {"first_name"=>"Alessandro", "last_name"=>"Sette", "scopus_author_id"=>"35418504700"}, {"first_name"=>"Miriam", "last_name"=>"Postan", "scopus_author_id"=>"6701908599"}, {"first_name"=>"Rick L.", "last_name"=>"Tarleton", "scopus_author_id"=>"7007130277"}], "year"=>2006, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"33748057802", "pui"=>"44299881", "isbn"=>"1553-7374 (Electronic)", "doi"=>"10.1371/journal.ppat.0020077", "issn"=>"15537366", "scopus"=>"2-s2.0-33748057802", "pmid"=>"16879036"}, "id"=>"fe9b8373-6cc6-39f8-bf4b-1c646fb67ba7", "abstract"=>"CD8+ T cells are crucial for control of a number of medically important protozoan parasites, including Trypanosoma cruzi, the agent of human Chagas disease. Yet, in contrast to the wealth of information from viral and bacterial infections, little is known about the antigen specificity or the general development of effector and memory T-cell responses in hosts infected with protozoans. In this study we report on a wide-scale screen for the dominant parasite peptides recognized by CD8+ T cells in T. cruzi-infected mice and humans. This analysis demonstrates that in both hosts the CD8+ T-cell response is highly focused on epitopes encoded by members of the large trans-sialidase family of genes. Responses to a restricted set of immunodominant peptides were especially pronounced in T. cruzi-infected mice, with more than 30% of the CD8+ T-cell response at the peak of infection specific for two major groups of trans-sialidase peptides. Experimental models also demonstrated that the dominance patterns vary depending on the infective strain of T. cruzi, suggesting that immune evasion may be occurring at a population rather than single-parasite level.", "link"=>"http://www.mendeley.com/research/cd8-tcell-responses-trypanosoma-cruzi-highly-focused-strainvariant-transsialidase-epitopes", "reader_count"=>52, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Student > Doctoral Student"=>6, "Researcher"=>5, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>6, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Student > Doctoral Student"=>6, "Researcher"=>5, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>6, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>7, "Immunology and Microbiology"=>9}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Argentina"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>1}

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  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/470953", "https://ndownloader.figshare.com/files/471006", "https://ndownloader.figshare.com/files/471055", "https://ndownloader.figshare.com/files/471109", "https://ndownloader.figshare.com/files/471118", "https://ndownloader.figshare.com/files/471135"], "description"=>"<div><p>CD8<sup>+</sup> T cells are crucial for control of a number of medically important protozoan parasites, including <em>Trypanosoma cruzi,</em> the agent of human Chagas disease<em>.</em> Yet, in contrast to the wealth of information from viral and bacterial infections, little is known about the antigen specificity or the general development of effector and memory T-cell responses in hosts infected with protozoans. In this study we report on a wide-scale screen for the dominant parasite peptides recognized by CD8<sup>+</sup> T cells in T. cruzi–infected mice and humans. This analysis demonstrates that in both hosts the CD8<sup>+</sup> T-cell response is highly focused on epitopes encoded by members of the large <em>trans</em>-sialidase family of genes. Responses to a restricted set of immunodominant peptides were especially pronounced in T. cruzi–infected mice, with more than 30% of the CD8<sup>+</sup> T-cell response at the peak of infection specific for two major groups of <em>trans</em>-sialidase peptides. Experimental models also demonstrated that the dominance patterns vary depending on the infective strain of <em>T. cruzi,</em> suggesting that immune evasion may be occurring at a population rather than single-parasite level.</p></div>", "links"=>[], "tags"=>["t-cell", "responses", "are", "focused", "strain-variant", "epitopes"], "article_id"=>152864, "categories"=>["Microbiology", "Cancer", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.0020077.sg001", "https://dx.doi.org/10.1371/journal.ppat.0020077.sg002", "https://dx.doi.org/10.1371/journal.ppat.0020077.sg003", "https://dx.doi.org/10.1371/journal.ppat.0020077.st001", "https://dx.doi.org/10.1371/journal.ppat.0020077.st002", "https://dx.doi.org/10.1371/journal.ppat.0020077.st003"], "stats"=>{"downloads"=>20, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/CD8_T_Cell_Responses_to_Trypanosoma_cruzi_Are_Highly_Focused_on_Strain_Variant_trans_Sialidase_Epitopes/152864", "title"=>"CD8<sup>+</sup> T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant <em>trans</em>-Sialidase Epitopes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2006-08-04 00:47:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/958508"], "description"=>"<div><p>(A) Venn diagram representing relative frequencies and overlap of T cells responding to T. cruzi epitopes. The blue shaded circles (left) show the high-abundance overlapping peptides TSKB21 and TSKB20, along with the low-abundance overlapping peptide TSKB260. These peptides are among the most highly represented H-2K<sup>b</sup>–binding peptides in the proteome and elicit the strongest CD8<sup>+</sup> T-cell response following infection with Brazil strain <i>T. cruzi,</i> as shown in (B). The smaller purple shaded circles (right) show the lower-abundance epitopes TSKB18, TSKB74, TSKB80, and TSKB89, which are recognized by T-cell populations that overlap minimally with TSKB20/21/260-specific T cells.</p><p>(B) Relative frequencies of CD8<sup>+</sup> T cells recognizing the TSKB20 (blue) and TSKB18 (purple) families of peptides in the acute (left) and chronic (right) phase of T. cruzi infection in mice infected with three different strains. While there are strain-dependent differences in the magnitude of the TSKB20-specific T-cell responses, these responses all follow a similar pattern of expansion and contraction during acute infection, which may be explained simply by strain-dependent differences in the rates of parasite replication and/or expression levels of TSKB20. However, T-cell responses to TSKB18 vary remarkably in both their magnitude and kinetics following infection with the various strains. Sustained expansion of TSKB18-specific T cells following infection with CL or Y strains results in different hierarchies of Ag-specific CD8<sup>+</sup> T cells in chronic infection with the three different strains (right).</p></div>", "links"=>[], "tags"=>["frequencies", "epitope", "occurrences", "genome", "t-cell"], "article_id"=>628529, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g006", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_Frequencies_of_Epitope_Occurrences_in_the_Genome_and_CD8_T_Cell_Responses_/628529", "title"=>"Relative Frequencies of Epitope Occurrences in the Genome and CD8<sup>+</sup> T-Cell Responses", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:36:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/958413"], "description"=>"<p>B6 mice were infected with 1,000 Brazil, 1,000 Y, or 10,000 CL strain T. cruzi and stained with TSKB20/K<sup>b</sup> (top) or TSKB18/K<sup>b</sup> (bottom) tetramers as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Data shown are a combination of two separate experiments with three or four mice per group per experiment.</p>", "links"=>[], "tags"=>["dominance", "patterns"], "article_id"=>628443, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parasite_Strain_Dependent_Dominance_Patterns_in_T_cruzi_8211_Infected_Mice_/628443", "title"=>"Parasite Strain–Dependent Dominance Patterns in T. cruzi–Infected Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:35:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/958253"], "description"=>"<div><p>(A) SCs from naive or chronically infected (Brazil) B6 mice were stained with TSKB20/K<sup>b</sup>-PE tetramers, then anti-CD8 APCs and a Cy5PE exclusion channel consisting of anti-CD4, anti-CD11b, and anti-B220. Cells shown are gated on Cy5PE<sup>neg</sup>lymphocyte<sup>+</sup> populations. Numbers represent the percentage of CD8<sup>+</sup> T cells staining with the TSKB20/K<sup>b</sup> tetramer.</p><p>(B) Kinetics of TSKB20 (closed triangles)– and TSKB18 (open triangles)–specific responses during Brazil strain infection of B6 mice. Data are representative of three experiments (<i>n</i> = 5 mice per group).</p><p>(C) SCs from infected mice were stained with anti-CD8–FITC, TSKB20/K<sup>b</sup>-PE, anti-CD4/11b/B220 cocktail, and either TSKB18/K<sup>b</sup>–APC (top) or TSKB21/K<sup>b</sup>–APC (bottom). Left panel shows CD8 versus TSKB20/K<sup>b</sup>; middle panel shows CD8 versus TSKB18/K<sup>b</sup> or TSKB21/K<sup>b</sup>; right panel shows TSKB18/K<sup>b</sup> or TSKB21/K<sup>b</sup> tetramer staining versus TSKB20/K<sup>b</sup> staining, gated on CD8<sup>+</sup> lymphocytes.</p></div>", "links"=>[], "tags"=>["cross-reactivity", "t-cell", "responses", "ts"], "article_id"=>628282, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Magnitude_Kinetics_and_Cross_Reactivity_of_CD8_T_Cell_Responses_to_Dominant_ts_Epitopes_/628282", "title"=>"Magnitude, Kinetics, and Cross-Reactivity of CD8<sup>+</sup> T-Cell Responses to Dominant ts Epitopes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:34:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/958353"], "description"=>"<p>PBMCs were stained using MHC tetramers specific for the TSA2–38 or TSA2–44 epitopes. The percentage of CD8<sup>+</sup> T cells staining positive for TSA2–38 is shown for a representative chronic chagasic patient and an uninfected control. Cells shown are lymphocytes gated on CD4<sup>neg</sup>B220<sup>neg</sup>CD11b<sup>neg</sup> lymphocytes. Five out of eight IFNγ ELISPOT<sup>+</sup> subjects stained positive with tetramers.</p>", "links"=>[], "tags"=>["lymphocytes", "recognizing", "ts", "epitopes", "patients", "chagas"], "article_id"=>628379, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_CD8_T_Lymphocytes_Recognizing_HLA_A2_1_8211_Restricted_ts_Epitopes_in_Patients_with_Chronic_Chagas_Disease_/628379", "title"=>"Detection of CD8<sup>+</sup> T Lymphocytes Recognizing HLA-A2.1–Restricted ts Epitopes in Patients with Chronic Chagas Disease", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:35:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/958173"], "description"=>"<div><p>(A) SCs from naive (gray bars) or chronically infected (Brazil strain; black bars) B6 mice were stimulated for 5 h with TSKB20, cruzipain, or GFT peptides plus GolgiPlug as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Data represent the number of CD8<sup>+</sup> T cells producing IFNγ; error bars represent SD.</p><p>(B) SCs from naive B6 mice were loaded with T. cruzi peptides and labeled with CFSE as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. The numbers above the peaks represent the percentage of specific killing of the target cells loaded with the indicated peptide and was calculated as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Data are representative of three experiments.</p></div>", "links"=>[], "tags"=>["responses", "murine", "cells", "directed", "non-ts"], "article_id"=>628205, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_Responses_of_Murine_CD8_T_Cells_Directed_against_Non_ts_Epitopes_/628205", "title"=>"Functional Responses of Murine CD8<sup>+</sup> T Cells Directed against Non-ts Epitopes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:33:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/958123"], "description"=>"<div><p>(A) SCs from naive (gray bars) or chronically infected (Brazil strain; black bars) B6 mice were stimulated overnight with ts peptides on anti-IFNγ–coated ELISPOT plates as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Error bars represent SD. Data represent the number of SFUs per 10<sup>6</sup> SCs plated.</p><p>(B) SCs from naive B6 mice were loaded with T. cruzi peptides and labeled with CFSE as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Cells were recovered from naive and infected mice 16 h after transfer and examined for CFSE fluorescence. The numbers above the peaks represent the percentage of specific killing for targets loaded with the respective peptide, and was calculated as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020077#s4\" target=\"_blank\">Materials and Methods</a>. Data are representative of eight experiments.</p></div>", "links"=>[], "tags"=>["responses", "murine", "cells", "directed", "ts"], "article_id"=>628157, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Diana L Martin", "D. Brent Weatherly", "Susana A Laucella", "Melissa A Cabinian", "Matthew T Crim", "Susan Sullivan", "Mark Heiges", "Sarah H Craven", "Charles S Rosenberg", "Matthew H Collins", "Alessandro Sette", "Miriam Postan", "Rick L Tarleton"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.0020077.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_Responses_of_Murine_CD8_T_Cells_Directed_against_T_cruzi_8211_Derived_ts_Peptides_/628157", "title"=>"Functional Responses of Murine CD8<sup>+</sup> T Cells Directed against T. cruzi–Derived ts Peptides", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:32:45"}

PMC Usage Stats | Further Information

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Relative Metric

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