Single-Cell Sequencing of T cell Receptors: A Perspective on the Technological Development and Translational Application
T cells recognize peptides bound to major histocompatibility complex (MHC) class I and class II molecules at the cell surface. This recognition is accomplished by the expression of T cell receptors (TCR) which are required to be diverse and adaptable in o
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Single-Cell Sequencing of T cell Receptors: A Perspective on the Technological Development and Translational Application Shivai Gupta, Richard Witas, Alexandria Voigt, Touyana Semenova, and Cuong Q. Nguyen
Abstract
T cells recognize peptides bound to major histocompatibility complex (MHC) class I and class II molecules at the cell surface. This recognition is accomplished by the expression of T cell receptors (TCR) which are required to be diverse and adaptable in order to accommodate the various and vast number of antigens presented on the MHCs. Thus, determining TCR repertoires of effector T cells is necessary to understand the immunological process in responding to cancer progression, infection, and autoimmune development. Furthermore, understanding the TCR repertoires will provide a solid framework to predict and test the antigen which is more critical in autoimmunity. However, it has
S. Gupta · A. Voigt · T. Semenova Department of Infectious Diseases and Immunology, College of Veterinary Medicine, Gainesville, FL, USA R. Witas Department of Oral Biology, College of Dentistry, Gainesville, FL, USA C. Q. Nguyen (*) Department of Infectious Diseases and Immunology, College of Veterinary Medicine, Gainesville, FL, USA Department of Oral Biology, College of Dentistry, Gainesville, FL, USA Center of Orphaned Autoimmune Diseases, University of Florida, Gainesville, FL, USA e-mail: nguyenc@ufl.edu
been a technical challenge to sequence the TCRs and provide a conceptual context in correlation to the vast number of TCR repertoires in the immunological system. The exploding field of single-cell sequencing has changed how the repertoires are being investigated and analyzed. In this review, we focus on the biology of TCRs, TCR signaling and its implication in autoimmunity. We discuss important methods in bulk sequencing of many cells. Lastly, we explore the most pertinent platforms in single-cell sequencing and its application in autoimmunity. Keywords
T cells · T cell receptors · T cell receptor signaling · Single cell sequencing · Bulk sequencing · Sjogren’s syndrome
3.1
Introduction
T cells are a critical component of the adaptive immune system capable of recognizing a nearly infinite variety of antigens. T cells recognize antigens through unique antigen receptors called T cell receptors (TCRs). Unlike the closely related B cell receptors (BCRs), which can secrete as an antibody, TCRs are strictly membrane bound and are not secreted [1, 2]. As a result, TCRs lack the opsonization and neutralization abilities of antibodies and are committed to
# Springer Nature Singapore Pte Ltd. 2020 B. Yu et al. (eds.), Single-cell Sequencing and Methylation, Advances in Experimental Medicine and Biology 1255, https://doi.org/10.1007/978-981-15-4494-1_3
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participating in antigen recognition followed by intracellular signaling and subsequent T cell activation [3]. TCRs are further distinguished from BCRs by their mechanisms for antigen recognition. While BCRs can directly bind to a wide variety of molecul
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