Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules
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Mendeley | Further Information

{"title"=>"Anchor side chains of short peptide fragments trigger ligand-exchange of Class II MHC molecules", "type"=>"journal", "authors"=>[{"first_name"=>"Shashank", "last_name"=>"Gupta", "scopus_author_id"=>"57054390900"}, {"first_name"=>"Sabine", "last_name"=>"Höpner", "scopus_author_id"=>"15757284500"}, {"first_name"=>"Bernd", "last_name"=>"Rupp", "scopus_author_id"=>"56920832400"}, {"first_name"=>"Sebastian", "last_name"=>"Günther", "scopus_author_id"=>"24449269900"}, {"first_name"=>"Katharina", "last_name"=>"Dickhaut", "scopus_author_id"=>"15757250800"}, {"first_name"=>"Noopur", "last_name"=>"Agarwal", "scopus_author_id"=>"21742241400"}, {"first_name"=>"M. Cristina", "last_name"=>"Cardoso", "scopus_author_id"=>"7103171689"}, {"first_name"=>"Ronald", "last_name"=>"Kühne", "scopus_author_id"=>"7007063778"}, {"first_name"=>"Karl Heinz", "last_name"=>"Wiesmüller", "scopus_author_id"=>"7006478708"}, {"first_name"=>"Günther", "last_name"=>"Jung", "scopus_author_id"=>"36037164600"}, {"first_name"=>"Kirsten", "last_name"=>"Falk", "scopus_author_id"=>"7102412633"}, {"first_name"=>"Olaf", "last_name"=>"Rötzschke", "scopus_author_id"=>"7003304342"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"46349107222", "doi"=>"10.1371/journal.pone.0001814", "pui"=>"351917376", "pmid"=>"18350151", "scopus"=>"2-s2.0-46349107222", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"509e7fbb-d477-3c34-8396-df83b5530bff", "abstract"=>"Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a 'non-receptive' state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the 'closure' of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important \"sensor\" for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way.", "link"=>"http://www.mendeley.com/research/anchor-side-chains-short-peptide-fragments-trigger-ligandexchange-class-ii-mhc-molecules", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Master"=>3, "Other"=>8, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Master"=>3, "Other"=>8, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>3, "Physics and Astronomy"=>2, "Chemistry"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Sweden"=>1, "United Kingdom"=>1, "French Polynesia"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/935653"], "description"=>"<p>The coordinates of the MHC component of the crystallized HLA-DR1/HA306-318 complex (1DHL) were used to carry out a 15 ns MD calculation with an ‘empty’ MHC molecule. a) Dynamic of the empty MHC molecule. The floor composed of the β-plated sheats is depicted in magenta, the α-helices of the starting structure are shown in red, α-helices of the structure obtained after 15 ns are shown in blue. The approximate position of P1 is indicated. While the dynamic was carried out with all extracellular domains, only the binding site is shown (α<sub>1</sub>-, β<sub>1</sub>-domain). b) Dynamic of the peptide-MLE stabilized MHC molecule. The same MD calculation was carried out as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone-0001814-g007\" target=\"_blank\">Fig. 7a</a> except that coordinates of an HLA-DR1 molecule were used, in which prior to the MD calculation the peptide-MLE Ac-FR-NH<sub>2</sub> was docked into the P1 pocket. c) P1 pocket in the peptide loaded MHC complex. The image shows a cross-section of the HLA-DR1/HA306-318 complex. The surface of the MHC molecule is shown in yellow, the peptide ligand in red; position of the P1 pocket is indicated. d) Loss of P1 in the empty MHC molecule. The same cross-section shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone-0001814-g007\" target=\"_blank\">Fig. 7c</a> for the peptide-loaded MHC is shown here for the empty molecule obtained after 15 ns of MD calculation. In this structure the P1 pocket can no longer be located.</p>", "links"=>[], "tags"=>["peptide-mle", "stabilized"], "article_id"=>606085, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g007", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_dynamic_MD_calculation_of_8216_empty_8217_and_peptide_MLE_stabilized_HLA_DR1_/606085", "title"=>"Molecular dynamic (MD) calculation of ‘empty’ and peptide-MLE stabilized HLA-DR1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:41:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/935086"], "description"=>"<p>To demonstrate that peptide-MLE can catalyze the reversible ligand exchange, complex dissociation of CLIP/HLA-DR1 induced by the peptide-MLE was determined in the absence (left panel) or presence of 200 µg/ml free HA306-318 (right panel). In this experiment 10 mM Ac-FR-NH<sub>2</sub>, (filled circle), Ac-YR-NH<sub>2</sub> (filled triangle), Ac-LR-NH<sub>2</sub> (open circle), Ac-AR-NH<sub>2</sub> (open triangle) or no catalysts (cross) was used. The percentage of CLIP/HLA-DR1 complex remaining after indicated time points was determined by ELISA.</p>", "links"=>[], "tags"=>["dipeptides", "reversible", "ligand"], "article_id"=>605519, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Catalytic_dipeptides_trigger_reversible_ligand_exchange_/605519", "title"=>"Catalytic dipeptides trigger reversible ligand exchange.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:31:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/935209"], "description"=>"<p>Recombinant soluble HLA-DR1 molecules were mutated inside the P1 pocket and used in loading experiments with ABL908-922, a peptide able to bind to wt as well as to the mutated forms of HLA-DR1 (S. Höpner, unpublished). Upper panels: the spontaneous loading of ABL908-922 is shown for wt HLA-DR1 (β86G), for HLA-DR1 (β86G→V) and HLA-DR1 (β86G→Y). The formation of ABL908-922/HLA-DR complex is expressed in counts per minute (cpm); dashed line indicates background signal. Lower panels: The allele-selective effect of catalytic dipeptides is shown. The influence on HLA-DR loading is shown for Ac-FR-NH<sub>2</sub> (filled circle), Ac-WR-NH<sub>2</sub> (filled triangle down), Ac-YR-NH<sub>2</sub> (filled square) and Ac-LR-NH<sub>2</sub> (open circle) and for p-chlorophenol (pCP; cross with dashed line), a simple aromatic MLE compound acting independent of P1 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone.0001814-MarinEsteban2\" target=\"_blank\">[13]</a>. 1.5 µg/ml ABL908-922 were used for wt HLA-DR1 and HLA-DR1 (β86G→V) and 0.2 µg/ml for HLA-DR1 (β86G→Y). Complex formation is expressed as relative enhancement in reference to the spontaneous complex formation in the absence of any catalyst. The loading was determined by ELISA.</p>", "links"=>[], "tags"=>["selectivity", "catalytic"], "article_id"=>605648, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_selectivity_of_catalytic_dipeptides_/605648", "title"=>"Allele selectivity of catalytic dipeptides.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:34:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/934926"], "description"=>"<p>a) Role of H-bonds for the catalytic activity of dipeptides. Various H-bond bridges proximal to the P1 pocket stabilize the ligand complex (compare <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone-0001814-g001\" target=\"_blank\">Fig. 1a</a>). N-terminal acetylation and C-terminal amidation was introduced to the YR dipeptide to facilitate the utilization of this H-bond network by minimal peptide-MLE catalysts. The influence was demonstrated in loading reactions with HA306-318 and sol. HLA-DR1 in the presence of titrated amounts of YR (filled circle), Ac-YR (open circle), YR-NH<sub>2</sub> (open triangle), Ac-YR-NH<sub>2</sub> (open square) and as control Ac-AR-NH<sub>2</sub> (open diamond). b) Impact of elongated side chain spacing. A dipeptide derivative was used in which the side chain spacing was elongated a single CH<sub>2</sub>-group by using the L-β-homotyrosine (Ac-b3hYR-NH<sub>2</sub>; open circle) instead of tyrosine (Ac-YR-NH<sub>2</sub>; filled circle). c) Influence of D-amino acids. Complex formation was carried out in the presence of titrated amounts of Ac-YR-NH<sub>2</sub> (filled circle), Ac-ry-NH2 (open circle), Ac-rY-NH<sub>2</sub> (open triangle), Ac-Ry-NH<sub>2</sub> (open square), Ac-yR-NH<sub>2</sub> (open diamond), Ac-Yr-NH<sub>2</sub> (open triangle up), Ac-yr-NH<sub>2</sub> (open hexagon). D-amino acids are indicated by small letters. d) Structural requirements of the catalytic anchor side chain. The P1 pocket of HLA-DR1 interacts preferably with bulky hydrophobic anchor side chains. To compare the catalytic activity with the known structural preferences of P1 the complex formation of HA306-318/HLA-DR1 is shown for Ac-FR-NH<sub>2</sub> (filled circle), Ac-WR-NH<sub>2</sub> (filled triangle down), Ac-YR-NH<sub>2</sub> (filled square), Ac-LR-NH<sub>2</sub> (open circle), Ac-MR-NH<sub>2</sub> (open triangle down), Ac-IR-NH<sub>2</sub> (open square), Ac-VR-NH<sub>2</sub> (open diamond), Ac-ER-NH<sub>2</sub> (open triangle up).</p>", "links"=>[], "tags"=>["relationships", "catalytic"], "article_id"=>605363, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g002", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_activity_relationships_of_catalytic_dipeptides_/605363", "title"=>"Structure/activity relationships of catalytic dipeptides.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:29:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/935408"], "description"=>"<p>a) Confocal laser scanning analysis of cell surface loading. 721.221-DRb1GFP cells expressing a GFP-tagged HLA-DR1 molecule were incubated with biotinylated HA306-318 peptide in the absence or presence of Ac-FR-NH<sub>2</sub>. After staining with streptavidin-Cy5 images were taken by confocal laser scanning microscopy. Scale bar represents 10 µm. b) Impact on APC loading and T cell response. Fibroblast transfectants expressing either wt HLA-DR1 (left panels) or mutated HLA-DR1 (β86G→V; right panels) were incubated with ABL908-922 in the presence of titrated amounts of Ac-FR-NH<sub>2</sub> (filled circle), Ac-WR-NH<sub>2</sub> (filled triangle), Ac-YR-NH<sub>2</sub> (filled square), Ac-LR-NH<sub>2</sub> (open circle) or in the absence of any peptide-MLE. Upper panels: Analysis of cell surface loading by FACS. Fibroblast cells were incubated with 12 µg/ml biotinylated ABL908-922. After 4h peptide loading was determined by FACS and is expressed as geometrical mean (geo. mean). Lower panels: Enhancement of the ABL908-922-specific T cell response. Fibroblast cells expressing wt HLA-DR1 or HLA-DR1 (β86G→V) were incubated for 4 h with 150 ng/ml or 300 ng/ml ABL908-922, washed and used to challenge SaABL1/G2, an ABL908-922 specific T cell hybridoma that recognizes the peptide on both HLA-DR1 molecules. The response is expressed as IL-2 release; dashed lines represent the T cell response triggered in the absence of any MLE compounds.</p>", "links"=>[], "tags"=>["loading", "mhc"], "article_id"=>605844, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enhanced_loading_of_cell_surface_MHC_by_peptide_MLE_/605844", "title"=>"Enhanced loading of cell surface MHC by peptide-MLE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:37:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/934773"], "description"=>"<p>a) Location of P1 and the H-bond network in class II MHC molecules. Left panel: top view on the peptide binding site of the class II MHC molecule HLA-DR1. Only the α<sub>1</sub>- (blue ribbon) and the β<sub>1</sub>-domain of the MHC molecule (red ribbon) are depicted; position of P1 is indicated. The backbone of the peptide ligand HA306-318 and the anchor side chain filling the P1 pocket are shown in yellow; MHC residues forming H-bonds with the backbone are labelled in grey. Right panel: side view of a P1 pocket loaded with the tyrosine anchor side chain. Surface of the pocket is indicated in yellow; amino acid residues forming this pocket are indicated; the peptide is shown in spacefill mode (green). Images are based on the crystal structure of HA306-318/HLA-DR1 (PDB: 1DLH) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone.0001814-Stern2\" target=\"_blank\">[38]</a>. b) The catalytic impact of dipeptide side chains on the formation of antigen-complexes. The influence of short peptides on the complex formation-rate between HA306-318 and soluble HLA-DR1 was determined. The loading reaction was carried out in the presence of titrated amounts of the dipeptides Tyr-Arg (YR, filled circle) or Ala-Arg (AR, open circle) or in the absence of these dipeptides (dashed line). Complex formation was determined by ELISA and is expressed as relative enhancement in reference to the spontaneous complex formation in the absence of any catalyst. The amount of catalytic peptide fragments (MLE concentration) is indicated on the x-axis.</p>", "links"=>[], "tags"=>["chains", "peptide", "fragments", "catalyze"], "article_id"=>605206, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amino_acid_side_chains_of_short_peptide_fragments_can_catalyze_the_formation_of_MHC_ligand_complexes_/605206", "title"=>"Amino acid side chains of short peptide fragments can catalyze the formation of MHC/ligand complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:26:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/935769"], "description"=>"*<p>‘Minimal peptide-MLE’ and ‘catalytic tripeptides’ are introduced in this study, catalytic activity for ‘invariant chain derived peptides’ has been reported for LRMK and LRMKLPK <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone.0001814-Xu1\" target=\"_blank\">[16]</a> and for LRKPPKPV <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001814#pone.0001814-Kropshofer2\" target=\"_blank\">[17]</a>.</p>**<p>The ‘Catalytic Rate Enhancement’ coefficient (<i>k</i>) represents the relative increase of the spontaneous loading rate (r<sub>spont</sub>) in the presence of the catalytic peptide (P<sub>cat</sub>). The total rate (r<sub>tot</sub>) can be calculated by (r<sub>tot</sub> = r<sub>spont</sub>+<i>k</i> [P<sub>cat</sub>] r<sub>spont</sub>).</p>***<p>“rel. cat. Activity” indicates the relative catalytic activity of peptide derivatives and is expressed as percentage in reference to the catalytic rate enhancement of Ac-FR-NH<sub>2</sub>.</p>", "links"=>[], "tags"=>["peptides", "loading", "soluble", "hla-dr1"], "article_id"=>606202, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.t001", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Catalytic_activity_of_short_peptides_on_the_loading_of_soluble_HLA_DR1_with_HA306_318_/606202", "title"=>"Catalytic activity of short peptides on the loading of soluble HLA-DR1 with HA306-318", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-03-19 01:43:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/460692"], "description"=>"<div><p>Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a ‘non-receptive’ state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the ‘closure’ of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important “sensor” for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way.</p></div>", "links"=>[], "tags"=>["anchor", "chains", "peptide", "fragments", "ligand-exchange", "ii", "mhc", "molecules"], "article_id"=>150779, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Anchor_Side_Chains_of_Short_Peptide_Fragments_Trigger_Ligand_Exchange_of_Class_II_MHC_Molecules/150779", "title"=>"Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-03-19 00:12:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/935512"], "description"=>"<p>a) Enhancement of the <i>in vitro</i> T cell response. The influence of catalytic peptides on the antigen-specific CD4+ T cell response was tested with a mouse T cell hybridoma EvHA/X5 (upper panels) and a human T cell line PD2 (lower panels). Both recognize the HA306-318 antigen in the context of HLA-DR1. The left panels show the influence of titrated amounts of Ac-FR-NH<sub>2</sub> (filled circle), Ac-YR-NH<sub>2</sub> (filled triangle) or Ac-LR-NH<sub>2</sub> (open circle) by EvHA/X5 and PD2 in the presence of 15 or 2 ng/ml HA306-318, respectively. The response in the absence any catalyst is indicated as a dashed line. The right panels are showing the dose response curves of HA306-318 in the presence of 5 mM Ac-FR-NH<sub>2</sub> (filled circle) or Ac-LR-NH<sub>2</sub> (open circle), 3 mM Ac-YR-NH<sub>2</sub> (filled triangle) or in the absence of any peptide-MLE (cross). Dashed line indicates the background. b) Enhancement of the <i>ex vivo</i> T cell response. Lymph node cells were isolated from HLA-DR1tg mice primed with HA306-318 peptide or NY-ESO-1 89-101. The <i>ex vivo</i> response was determined by an IFN-γ ELISPOT assay by challenging the cells with 5 ng/ml HA306-318 (upper panel) or 50 ng/ml NY-ESO-1 89-101 (lower panel), respectively. The bars represent the number of spots detected in the absence (black bar) or presence of 2.5 mM Ac-FR-NH<sub>2</sub> (grey bar). Each spot originates from a single IFN-γ secreting cell; dashed line indicates the background signal.</p>", "links"=>[], "tags"=>["antigen-specific"], "article_id"=>605948, "categories"=>["Immunology"], "users"=>["Shashank Gupta", "Sabine Höpner", "Bernd Rupp", "Sebastian Günther", "Katharina Dickhaut", "Noopur Agarwal", "M. Cristina Cardoso", "Ronald Kühne", "Karl-Heinz Wiesmüller", "Günther Jung", "Kirsten Falk", "Olaf Rötzschke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001814.g006", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amplification_of_the_antigen_specific_T_cell_response_/605948", "title"=>"Amplification of the antigen-specific T cell response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-03-19 01:39:08"}

PMC Usage Stats | Further Information

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Relative Metric

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