T cells recognize the VH complementarity-determining region 3 of the idiotypic protein of B cell non-Hodgkin's lymphoma.
The idiotypic protein expressed by B lymphoma cells is a clone-specific tumor antigen which may be suitable for immune targeting by T cells. In this study, we cloned the immunoglobulin heavy chain variable gene (VH) of the idiotypic protein from a patient with B cell lymphoma and used a synthetic peptide of 22 amino acids corresponding to the VH complementarity-determining region (CDR)-3 of the idiotypic protein to investigate whether autologous T cells could recognize this unique peptide. We demonstrated that autologous T cells possessing both CD4+ and CD8+ phenotypes could be propagated. The T cells were able to proliferate, secrete cytokines, and lyse autologous cells presensitized with the specific peptide in a major histocompatibility complex-dependent manner. Moreover, these CDR3 peptide-primed T cells were also able to kill autologous lymphoma cells. Our results therefore offer new perspectives for specific therapeutic vaccination for the treatment of B cell lymphoma.
Wen
Y J
YJ
Department of Haematology, University of Wales College of Medicine, Cardiff, GB.
Lim
S H
SH
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm / Q000276:immunology; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D005784:Gene Amplification; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; C044203:anti-IgM; D007371:Interferon-gamma