Basic and Clinical Aspects of the T-cell Receptor in Mature T-cell Malignancies

During T-cell development, thymocytes undergo a sequence of immunophenotypic and immunogenotypic changes resulting in the formation of mature T cells with receptors that recognize antigens with high specificity: the T-cell receptor (TCR). Recombination processes underlie the generation of the antigen-specificity of TCR molecules. The central theme of this thesis constitutes the basic aspects of V(D)J recombination of TCR genes and the diagnostic applications of the TCR in mature T-cell malignancies. The BIOMED-2 multiplex polymerase chain reaction (PCR) primers and protocols have been developed for the detection of immunoglobulin (Ig) and TCR gene rearrangements in human lymphoid cells. Using these assays we studied TCR diversity (repertoire) formation during T-cell development in human T lymphocytes. In addition, TCR gene rearrangement analysis was performed in malignant lymphoproliferations to determine its clinical diagnostic relevance, as well as to gain insight into the pathogenesis of mature T-cell malignancies.