The epitope in the frame region (FR) of the immunoglobulin heavy chain variable region (IgHV) is a potential target for lymphoma immunotherapy. Our previous work identified a FR-derived nonapeptide (QLVQSGAEV) capable of in vitro eliciting anti-lymphoma specific cytotoxic T lymphocytes (CTLs) in lymphocytes from human leukocyte antigen (HLA)-A2.1 donors. Here we used HLA-A2.1 transgenic mice and SCID (severe combined immunodeficiency) mice to confirm the ability of these specific CTLs against lymphomas. We immunized transgenic mice with nonapeptide conjugated to the adjuvant of PADRE (pan HLA DR-binding epitope). The specificity of the elicited CTLs from the immunized transgenic mice was identified by enzyme-linked immunospot (ELISpot) assay and pentamer staining. The elicited CTLs specifically attacked lymphomas with surface IgHV1 in vitro. Adoptive transfer of the CTLs to SCID mice loaded with QLVQSGAEV(+)/HLA-A2.1(+) lymphoma cells effectively inhibited tumor growth. Our results indicate that the relatively constant epitope in the IgHV FR may be useful for immunotherapy of lymphomas with the same IgHV subfamily.