Molecular analysis of T-cell receptor V beta chains of human T-cell chronic
lymphocytic leukemia does not show intraclonal variability: implications
for immunotherapy
F Picard, T Martin, F Legras, B Lioure and JL Pasquali
Laboratoire d'Immunopathologie, Hopital Central, Hopitaux Universitaires de
Strasbourg, France.
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.
Volume 82,
Issue 7,
pp. 2152-2156,
10/01/1993
Copyright © 1993 by The American Society of Hematology