T-cell receptor repertoires utilized in response to linear peptides representing an immunodominant MHC class II restricted T-cell epitope are far more diverse than that utilized in response to the same epitope in the nominal antigen.

Previous analyses of the T-cell receptor (TCR) repertoire utilized in response to the 1-102 fragment of the lambda cI repressor protein and specific for the immunodominant amino acid 12-26 region in the context of I-Ek, have shown this repertoire to be extremely restricted. In contrast, here we show that the TCR repertoires utilized in two strains of I-Ek expressing mice in response to two linear peptides representing this immunodominant region are diverse. Despite their extensive diversity, these repertoires are somewhat overlapping. In addition, structural similarities were observed between the full lambda cI fragment (1-102) and peptide elicited TCR repertoires, including frequent use of the Valpha2 family of gene segments, particularly among peptide (12-26) elicited TCRs cross-reactive with 1-102/I-Ek. Nevertheless, these data indicate that it may be difficult to mimic the immune response to an immunodominant epitope of a protein antigen via immunization with linear peptides containing the amino acid sequence of that epitope. Possible explanations for differences in the levels of TCR diversity among T cells responding to an epitope present in a nominal antigen as compared to T cells responding to linear peptide antigens containing this same epitope are discussed.