Abstract
The peculiarity of T cell is their ability to recognize an infinite range of self and foreign antigens. This ability is achieved during thymic development through a complex molecular mechanism based on somatic recombination that leads to the expression of a very heterogeneous population of surface antigen receptors, the T Cell Receptors (TCRs). TCRs are cell specific and represent a sort of “molecular tag” of T cells and have been widely studied to monitor the dynamics of T cells in terms of clonality and diversity in several contexts including lymphoid malignancies, infectious diseases, autoimmune diseases, and tumor immunology. In this review, we provide an overview of the strategies used to investigate the TCR repertoire from the pioneering techniques based on the V segments identification to the revolution introduced by Next-Generation Sequencing that allows for high-throughput sequencing of alpha and beta chains. Single cell based approaches brought the analysis to a higher level of complexity and now provide the opportunity to sequence paired alpha and beta chains. We also discuss novel approaches that through the integration of TCR tracking and mRNA single cell sequencing offer a valuable tool to associate antigen specificity to transcriptional dynamics and to understand the molecular mechanisms of T cell plasticity.
Highlights
Human T cells develop in the thymus from progenitors originating in hematopoietic tissues
The vast majority of human T cells express T Cell Receptors (TCRs) composed of α and β chains while a small subset expresses TCR composed of γ and δ chains. αβ T cells are key mediators of the adaptive immunity and recognize antigens presented in association to major histocompatibility complex (MHC) Class I and Class II proteins. γδ T cells instead are not MHC-restricted and are involved in “innate like” responses in tissues. αβ T cells represent more than 90% of the total T cell population and are more diversified compared to γδT; for this reason the vast majority of the studies to characterize TCR [1] are focused on αβ T cells
Pioneering experiments to dissect the T cell repertoire were performed at protein level using flow cytometry and a combination of monoclonal antibodies against the TCRBV subgroups
Summary
Human T cells develop in the thymus from progenitors originating in hematopoietic tissues. During their development, they acquire the ability to recognize foreign antigens and provide protection against many different pathogens. They acquire the ability to recognize foreign antigens and provide protection against many different pathogens This functional flexibility is guaranteed by the expression of highly polymorphic surface receptors called T cell receptors (TCRs). The vast majority of human T cells express TCRs composed of α (alpha) and β (beta) chains while a small subset expresses TCR composed of γ (gamma) and δ (delta) chains. Αβ T cells are key mediators of the adaptive immunity and recognize antigens presented in association to major histocompatibility complex (MHC) Class I and Class II proteins. The enormous diversity of T cell repertoires is generated by random combinations of germ line gene segments
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