Lymphoma-derived
immunoglobulin idiotype (Id) is a tumour-specific
antigen used for antitumour vaccination in
follicular lymphoma (FL). However, FL Ids are subject to hypermutation and subclones may escape antitumour cytotoxic T-cell response. To investigate the intraclonal
epitope diversity, we sequenced the FL heavy chain gene (consensus Id gene) and subclones of 24 patients. The derived
polypeptide sequences were analysed by bioinformatics for human leucocyte
antigen (HLA)-A0201-restricted
epitope prediction.
Epitopes were classified according to BIMAS and SYFPEITHI scores. Surprisingly in these highly mutated
polypeptides, the
epitopes concentrated in short hotspots in the conserved framework regions (FRs), both in HLA-A0201(+) and HLA-A0201(-) patients. Similar hotspots have been observed by others in chronic lymphocytic leukaemia Ids which in contrast to FL have low mutation frequency. FR3
amino acids 78-88 displayed the best-score
epitopes in Ids containing a VH3-family segment, the most represented in FL Ids. Such VH3-FR3(78-88)
epitopes were previously demonstrated as immunogenic. Modifications of the
epitope pattern in subclones of HLA-A0201(+) patients were generally absent from high-score
peptides, including VH3-FR3(78-88)
epitopes (83% unmodified). Therefore, no tendency for loss of HLA-A0201-restricted
epitopes was evidenced and, given their limited intraclonal diversity, VH3-FR3(78-88)
epitopes may provide a useful target for the induction of cytotoxic response in Id-vaccinated FL patients.