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Update of cell repertoire studies in hematology Volume 3, issue 3, Mai-Juin 1997

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In this review we first present the main mechanisms developed by the immune system to generate different levels of diversity among TCR ab T cells and the means to analyze such diversity. We then describe how such analyses can be used as diagnostic tools or monitoring tools in clinical situations. Among healthy donors, comparison of ab repertoire within peripheral blood demonstrate both some reproducible features (TCR-Vb frequencies among total peripheral CD3+ is remarkably similar between individuals) and some heterogeneity (for example, clonal expansions are frequently observed within the CD8+CD45RO+ subset). New technical approaches, called Immunoscope or Spectratyping, allow an overall estimation of ab T cell repertoire diversity through numerous determination (200 to 2 000) of junction size heterogeneity within each of the TCR-Vb subsets. These methods also provide a way to detect oligoclonal or amplified TCR-Vb subsets. Together with the use of a large panel of monoclonal antibodies directed at specific TCVb subsets they allow the detection and purification of T cells potentially reactive against malign proliferation, as previously shown in a case of a B-LLC. Such strategies, which take advantage of both structural and functional approaches will be helpful in finding new tumoral antigens and in understanding why tumor specific T cells fail to control tumor growth. Regarding bone marrow transplantation, T cell repertoire studies performed within the first months following transplantation have evidenced numerous clonal expansions, some of them related to the graft versus host disease process. Finally, the finding of major and long-lasting clonal expansions years after transplantation raises the question of the origin and the regulation of these amplified T cell subsets.