The molecular context of determinants within the priming antigen establishes a hierarchy of T cell induction: T cell specificities induced by peptides of beta-galactosidase vs. the whole antigen.
The antibody response following priming with a macromolecule or a peptide will depend on the regulatory T cells that become activated by the antigenic determinants available. In this report, activation of T helper (Th) and T suppressor (Ts) cells by determinants on beta-galactosidase (GZ) was examined by comparing native GZ [1023 amino acid (a.a.) residues per monomer] with peptides from the immunodominant region encompassing residues 3 to 187. Each immunogen established its characteristic hierarchy of dominance of determinants within it: in particular, GZ and CB-2-3 (a.a. 3-187) each induced immunodominant Th cells which could not be induced by T8 (a.a. 60-140). Hierarchies of suppressor determinant are also created: T8-Ts suppresses all Th specificities and therefore can be deemed immunodominant: T8-2-Ts and T8-3-Ts have a more selective suppressor activity and can be considered subdominant. We conclude that the outcome of immunization shifts with a change in the nature of the immunogen and the context within which the determinant lies will crucially influence its expression. A particular "context" presumably determines the likely order of processing of that molecule which leads to a characteristic relationship among the Ts, Th and B cell determinants involved.
Shivakumar
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Department of Biology, Catholic University of America, Washington, DC.
Sercarz
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Krzych
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes; D005696:Galactosidases / Q000276:immunology*; D007108:Immune Tolerance; D008211:Lymphocyte Cooperation; D051379:Mice; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D001616:beta-Galactosidase / Q000276:immunology*
D000939:Epitopes; D010446:Peptide Fragments; D005696:Galactosidases; D001616:beta-Galactosidase