T cell clonality assessment: past, present and future

Abstract

T cell clonality testing has important clinical and research value, providing a specific and reproducible assessment of clonal diversity in T cell proliferations. Here we review the conceptual foundations of T cell clonality assays, including T cell ontogeny and T cell receptor structure and function; we also provide an introduction to T cell receptor genomics and the concept of the T cell clonotype. This is followed by a review of historical and current methods by which T cell clonality may be assayed, including current assay limitations. Some of these assay limitations have been overcome by employing next-generation sequencing (NGS)-based technologies that are becoming a mainstay of modern molecular pathology. In this vein, we provide an introduction to NGS technologies, including a review of the preanalytical, analytical and postanalytical technologies relevant to T cell clonality NGS assays.

Keywords: genetics; lymphocytes; molecular pathology; oncology.

Figure 1

Schematic of TCR gene rearrangement. The schema begins in the germline configuration, followed by D-J gene rearrangement and finally by V-DJ gene rearrangement. The rearranged TCR configuration is then transcribed and translated into a protein monomer, which is paired with its monomer protein counterpart to form a functional TCR.