Insights on the amino acid side-chain interactions of a synthetic T-cell determinant

Borrás‐Cuesta, Francisco; Golvano, José; Sarobe, Pablo; Lasarte, Juan José; Prieto, Isidro; Szabó, Angela E.; Guillaume, Jean; Guillet, J.-G.

doi:10.1016/1045-1056(91)90033-g

Cited by 41 publications

(20 citation statements)

References 23 publications

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“…Thirty-five 15-mer peptides from hepatitis C virus core protein genotype 1b [35] were synthesized manually by the solid phase method of Merrifield [36] using the Fmoc alternative [37] and a multiple solid phase peptide synthesizer [38]. Peptide HA(306 -320) (CPKYVKQNTL KLATG) from Influenza A/Texas/77 virus hemagglutinin was synthesized manually, and biotinylated (while still attached to the resin) with an excess of N-hydroxysuccinimide-conjugated biotin (NH-LC-biotin) (Pierce).…”

Section: Materials and Methods Peptide Synthesismentioning

confidence: 99%

Specific and general HLA-DR binding motifs: comparison of algorithms

et al. 2000

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Using panels of peptides well characterized for their ability to bind to HLA DR1, DRB1*1101, or DRB1*0401 molecules, algorithms were deduced to predict binding to these molecules. These algorithms consist of blocks of 8 amino acids containing an amino acid anchor (Tyr, Phe, Trp, Leu, Ile, or Val) at position i and different amino acid combinations at positions i؉2 to i؉7 depending on the class II molecule. The sensitivity (% of correctly predicted binder peptides) and specificity (% of correctly predicted non-binder peptides) of these algorithms, were tested against different independent panels of peptides and compared to other algorithms reported in the literature. Similarly, using a panel of 232 peptides able to bind to one or more HLA molecules as well as 43 non-binder peptides, we deduced a general motif for the prediction of binding to HLA-DR molecules. The sensitivity and specificity of this general motif was dependent on the threshold score used for the predictions. For a score of 0.1, the sensitivity and specificity were 84.7% and 69.8%, respectively. This motif was validated against several panels of binder and non-binder peptides reported in the literature, as well as against 35, 15-mer peptides from hepatitis C virus core protein, that were synthesized and tested in a binding assay against a panel of 19 HLA-DR molecules. The sensitivities and specificities against these panels of peptides were similar to those attained against the panels used to deduce the algorithm. These results show that comparison of binder and non-binder peptides, as well as correcting for the relative abundance of amino acids in proteins, is a useful approach to deduce performing algorithms to predict binding to HLA molecules.

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Section: Materials and Methods Peptide Synthesismentioning

confidence: 99%

Specific and general HLA-DR binding motifs: comparison of algorithms

et al. 2000

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“…21. At the end of the synthesis, peptides were cleaved, deprotected, and washed six times with diethyl ether.…”

Section: Peptidesmentioning

confidence: 99%

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

Casares

Arribillaga

Sarobe

et al. 2003

The Journal of Immunology

193

147

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CD25+ regulatory T (T reg) cells suppress the activation/proliferation of other CD4+ or CD8+ T cells in vitro. Also, down-regulation of CD25+ T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25+ T reg cells allows the host to induce both CD4+ and CD8+ antitumoral responses following tumor challenge. Simultaneous depletion of CD25+ and CD8+ cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4+ T cells, which emerged in the absence of CD25+ T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4+ T cells was dependent on IFN-γ production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25+ T reg cells is restored over time. However, CD25+ T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25+ T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25+ T reg on the induction of long-lasting cellular immune responses.

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“…Peptide p1215, which encompasses an immunodominant cytotoxic T cell epitope within NS3 [17], was synthesized by the solid phase method using a multiple synthesizer as previously described [43], analyzed by HPLC and used without further purification.…”

Section: Ns3 Recombinant Protein and Peptide Synthesismentioning

confidence: 99%

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Arribillaga

Sarobe

Arina

et al. 2005

Vaccine

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The induction of protective or therapeutic cellular immunity against hepatitis C virus (HCV) is a difficult goal. In a previous work we showed that immunization with a recombinant adenovirus encoding HCV-NS3 (RAdNS3) could partially protect mice from challenge with a vaccinia virus encoding HCV antigens. We sought to investigate whether systemic administration of an immunostimulatory monoclonal antibody directed against the lymphocyte surface molecule CD137 could enhance the immunity elicited by RAdNS3. It was found that treatment with anti-CD137 mAb after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T helper cell responses against HCV NS3. Importantly, the ability of RAdNS3 to induce protective immunity against challenge with a recombinant vaccinia virus expressing HCV proteins was markedly augmented. Thus, combination of immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV proteins might be useful in strategies of immunization against HCV.

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Insights on the amino acid side-chain interactions of a synthetic T-cell determinant

Cited by 41 publications

References 23 publications

Specific and general HLA-DR binding motifs: comparison of algorithms

Specific and general HLA-DR binding motifs: comparison of algorithms

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

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