The molecular context of determinants within the priming antigen establishes a hierarchy of T cell induction: T cell specificities induced by peptides of β‐galactosidase <i>vs.</i> the whole antigen

Abstract

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.