Molecular analysis of T-cell receptor V beta chains of human T-cell chronic lymphocytic leukemia does not show intraclonal variability: implications for immunotherapy.
Human T-cell chronic lymphocytic leukemia (T-cell CLL) is a heterogeneous disease characterized by a monoclonal malignant proliferation of T cells in which the T-cell receptors (TCRs) can be, when expressed, considered to be membrane tumor-specific antigens. Owing to the increasing number of available monoclonal antihuman TCR reagents, it could be of interest to evaluate the feasibility of anti-TCR treatment during T-cell CLL. To test the therapeutic potentiality of anti-TCR monoclonal antibodies, we first analyzed the intraclonal variability in two terminally ill patients suffering from TCR alpha beta-positive cell CLL bearing different immunophenotypes. The cDNA corresponding to the variable regions of the TCR beta chains originating from the malignant T cells were amplified, cloned into M13 phages, and sequenced. The sequence analysis of multiple independent clones showed no intraclonal variability, with no evidence for ongoing hypermutation in the V beta region genes. The relevance of these findings with regard to an anti-V beta therapy and the comparison with similar analysis during B-cell monoclonal lymphoproliferations are discussed.
Laboratoire d'Immunopathologie, Hôpital Central, Hôpitaux Universitaires de Strasbourg, France.
F
F
Picard
T
T
Martin
F
F
Legras
B
B
Lioure
J L
JL
Pasquali
D015703:Antigens, CD / Q000097:blood; D001483:Base Sequence; D017252:CD3 Complex / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D014644:Genetic Variation; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D015461:Leukemia, Prolymphocytic, T-Cell / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta