Antigenic requirements for T-cell activation: reconstitution of a functional antigen from an inactive peptide portion of an antigen conjugated to protein carriers.
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.
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000032:analysis*; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D009842:Oligopeptides / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011506:Proteins / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D009842:Oligopeptides; D010446:Peptide Fragments; D011506:Proteins; C049909:tobacco mosaic virus protein (103-112)