Different properties of T-cell epitopes within complementarity-determining regions 1 and 2 of idiotypic VH in B-lymphoma

The idiotypic protein expressed by B-lymphoma cells can evoke an autologous idiotype-specific T-cell response in both animal studies and lymphoma patients. However, the locations within the idiotypic protein of the immune epitopes remains unclear. In this study, we determined the nature of any immune responses generated by peptides corresponding to the complementarity-determining region 1 (CDR1) and complementarity-determining region 2 (CDR2) sequences of idiotypic heavy chain variable region (VH) to identify the clinical potential of the peptides for immunotherapy of lymphoma. We found that a synthetic peptide corresponding to CDR1 sequence contains a functional T-cell epitope able to evoke a major histocompatibility complex (MHC) class II-dependent T-cell proliferative response and cytokine release without direct cytotoxicity for peptide-pulsed target or fresh autologous lymphoma cells. Although a peptide corresponding to CDR2 was able to generate MHC class I and class II dependent T-cell proliferative responses and cytokine release, T-cell epitopes within the peptide were cryptic in the context of intact idiotypic protein. Our results therefore suggest that the CDR1 sequence could be used for the immune targeting of B-lymphoma