The B cell immune response to an idiotype-inducing peptide epitope can be inhibited by immunodominance of a neighboring epitope.

Abstract

Three synthetic peptides, EEYEYE (peptide 1), EEYEYEEEYEYE (peptide 2), and YEEEEY (peptide 3), were tested for their ability to induce common Id that had been previously characterized for murine antibodies specific to random synthetic polymers of glutamic acid, alanine, and tyrosine ((Glu,Ala,Tyr)n) (cGAT Id). Protein conjugates of either peptide 2 or peptide 3, but not peptide 1, induced cGAT Id. This unique approach directly identified two peptides capable of inducing cGAT Id antibodies. Previous immunization with peptide 1-protein conjugate inhibited the cGAT Id response to peptide 2 conjugated to a different protein carrier. Thus, a neighboring or overlapping epitope can be used to inhibit a cGAT Id-inducing epitope without the participation of carrier-specific Ts and without using anti-Id antibodies. In contrast, previous immunization with peptide 1-protein conjugate did not inhibit cGAT Id induction by peptide 3-protein conjugate or by (Glu,Ala,Tyr)n. This ruled out the participation of Id-specific Ts cells. The effectiveness of inhibition coincided with the avid binding of anti-peptide 1 antibodies to peptide 2, which was > 10 and 100 times stronger than the binding to peptide 3 and (Glu,Ala,Tyr)n, respectively. We hypothesize that the primed peptide 1-specific B cells capture and process peptide 2-protein efficiently and act as APC to Th cells specific to the protein of the challenging Ag, resulting in the selective and dominant activation of peptide 1-specific B cells. Thus, our data suggest that epitope priming can inhibit an Id response to a neighboring epitope by a mechanism of clonal dominance.