Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia.
We have previously shown that autologous T cells recognize leukaemic cells from patients with chronic lymphocytic leukaemia (B-CLL) in an MHC class I- and/or II-restricted manner. A candidate recognition structure might be the tumour cell-derived Ig VH complementarity-determining region (CDR)3. Three patients with B-CLL were analysed for the presence of autologous T cells recognizing the tumour-specific VH-CDR3 region. The VH region was shown to be mutated in all three patients. In two patients, a VH-CDR3-specific T-cell response was detected by proliferation assay, as well as by gamma-interferon (IFN) production. The responses could be inhibited by monoclonal antibodies against MHC class II, but not MHC class I. In the third patient, a VH-CDR3 proliferative response was detected, which could be inhibited by an anti-MHC class I monoclonal antibody, but not by anti-MHC class II antibodies. No gamma-IFN response could be detected in this patient. In no patient was an interleukin (IL)-4 response noted. Thus, in patients with B-CLL, naturally occurring T cells recognizing the tumour-unique VH-CDR3 region are present.
Rezvany
M R
MR
Immune and Gene Therapy Laboratory, CCK, Stockholm.
Jeddi-Tehrani
M
M
Rabbani
H
H
Rudén
U
U
Hammarström
L
L
Osterborg
A
A
Wigzell
H
H
Mellstedt
H
H
D000368:Aged; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D005260:Female; D005803:Genes, Immunoglobulin; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D007371:Interferon-gamma