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Review
. 2023 Apr 14:14:1127470.
doi: 10.3389/fimmu.2023.1127470. eCollection 2023.

Antigen-specificity measurements are the key to understanding T cell responses

Rashmi Tippalagama  1 , Leila Y Chihab  1 , Kendall Kearns  1 , Sloan Lewis  1 , Sudhasini Panda  1 , Lisa Willemsen  1 , Julie G Burel  1 , Cecilia S Lindestam Arlehamn  1
Affiliations
Review

Antigen-specificity measurements are the key to understanding T cell responses

Rashmi Tippalagama et al. Front Immunol. .

Abstract

Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease.

Keywords: T cell; TCR; adaptive immunity; antigen-specificity; sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Methods to identify antigen-specificity. pMHC multimers allows the direct identification of antigen-specific T cells, while indirect methods rely on cytokine production, surface marker expression or cell proliferation upon in vitro stimulation. Created with BioRender.com.
Figure 2
Figure 2
Antigen-specific TCR repertoire using in vitro culture. Cells are stimulated with antigens or epitope pools. Only those clonotypes that expanded upon stimulation compared to ex vivo T cell samples across both replicates are analyzed further. The clonotypes are overlapped to obtain antigen-specific clonotypes. Clonotypes that expand in response to multiple unrelated stimuli are excluded.
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References

    1. Eisen HN, Chakraborty AK. Evolving concepts of specificity in immune reactions. Proc Natl Acad Sci USA (2010) 107(52):22373–80. doi: 10.1073/pnas.1012051108 - DOI - PMC - PubMed
    1. Schwartz RS. Diversity of the immune repertoire and immunoregulation. N Engl J Med (2003) 348(11):1017–26. doi: 10.1056/NEJMsa022766 - DOI - PubMed
    1. Lemke H. Immune response regulation by antigen receptors’ clone-specific nonself parts. Front Immunol (2018) 9:1471. doi: 10.3389/fimmu.2018.01471 - DOI - PMC - PubMed
    1. Burnet FM. A modification of jerne’s theory of antibody production using the concept of clonal selection. CA Cancer J Clin (1976) 26(2):119–21. doi: 10.3322/canjclin.26.2.119 - DOI - PubMed
    1. van Stipdonk MJ, Lemmens EE, Schoenberger SP. Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat Immunol (2001) 2(5):423–9. doi: 10.1038/87730 - DOI - PubMed

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