Antigenic requirements for T-cell activation: reconstitution of a functional antigen from an inactive peptide portion of an antigen conjugated to protein carriers |
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| Authors: | A M Wan B C Langton M L Andria E Benjamini |
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| Affiliation: | 1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Gordon Street, London WC1H 0AH, UK;2. Biomanufacturing Science Group, Pfizer Global Supply, Pearl River, New York;3. Biomanufacturing Science Group, Pfizer Global Supply, Strängnäs, Sweden;4. Biomanufacturing Science Group, Pfizer Global Supply, New York City, New York;1. Grupo de Pesquisa em Fotoquímica Orgânica Aplicada, Universidade Federal do Rio Grande do Sul - Instituto de Química, Avenida Bento Gonçalves 9500, CEP 91501-970 Porto Alegre, RS, Brazil;2. University of Campinas, Chemistry Institute, Campinas, São Paulo, Brazil;3. Universidade do Extremo Sul Catarinense - UNESC, Av. Universitária 1105, CEP 888806-000 Criciúma, SC, Brazil;4. University of São Paulo, São Carlos Institute of Chemistry, São Carlos, São Paulo, Brazil;5. Universidade Federal de Santa Catarina (UFSC), Rua João Pessoa 2750, CEP 89036-256 Blumenau, SC, Brazil;1. Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium;2. University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Section for Biologics, Universitetsparken 2, 2100 Copenhagen O, Denmark;3. Université Catholique de Louvain, Molecules, Solids and Reactivity, Institute of Condensed Matter and Nanosciences, 1348 Louvain-la-Neuve, Belgium;4. Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale, Pole of Pharmacology and Therapeutics, 1200 Brussels, Belgium |
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| Abstract: | The structural features of an antigenic peptide required for T-cell activation were examined by a novel approach: an active antigen was constructed from an inactive peptide portion of the original antigen by conjugating it to various proteins. An eicosapeptide, peptide 8, representing residues 103-112 of the tobacco mosaic virus protein (TMVP), was utilized as the model antigen for these studies. While peptide 8 was able to stimulate, in vitro, T-cells from peptide 8 primed mice, synthetic peptides representing various portions of peptide 8 were unable to activate these cells. Although the amino-terminal undecapeptide of peptide 8 (residues 93-103 of TMVP) was unable to activate T-cells from peptide 8 primed mice, conjugates which consisted of this undecapeptide coupled to certain proteins were capable of inducing antigen-specific proliferation of these T-cells. These results identify two structural antigenic features essential for T-cell activation: a T-cell-recognizable epitope within the amino-terminal undecapeptide of peptide 8 and a second region provided by the carboxy-terminal half of peptide 8 or by protein carriers. Potential roles for this second region include providing a site for antigen interaction with Ia molecules on the antigen-presenting cell or, alternatively, providing amino acids important in stabilizing the binding of the T-cell antigen receptor. The results suggest that the recognition of this second region exhibits only a limited specificity. |
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