Trogocytic molting of T cell microvilli upregulates T cell receptor surface expression and promotes clonal expansion

Jeong-Su Park, Jun-Hyeong Kim, Won-Chang Soh, Na-Young Kim, Kyung-Sik Lee, Chang-Hyun Kim, Ik-Joo Chung, Sunjae Lee, Hye-Ran Kim () and Chang-Duk Jun ()
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Jeong-Su Park: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Jun-Hyeong Kim: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Won-Chang Soh: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Na-Young Kim: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Kyung-Sik Lee: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Chang-Hyun Kim: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Ik-Joo Chung: Chonnam National University Medical School
Sunjae Lee: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Hye-Ran Kim: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)
Chang-Duk Jun: School of Life Sciences, Gwangju Institute of Science and Technology (GIST)

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract Although T cell activation is known to involve the internalization of the T cell antigen receptor (TCR), much less is known regarding the release of TCRs following T cell interaction with cognate antigen-presenting cells. In this study, we examine the physiological mechanisms underlying TCR release following T cell activation. We show that T cell activation results in the shedding of TCRs in T cell microvilli, which involves a combined process of trogocytosis and enzymatic vesiculation, leading to the loss of membrane TCRs and microvilli-associated proteins and lipids. Surprisingly, unlike TCR internalization, this event results in the rapid upregulation of surface TCR expression and metabolic reprogramming of cholesterol and fatty acid synthesis to support cell division and survival. These results demonstrate that TCRs are lost through trogocytic ‘molting’ following T cell activation and highlight this mechanism as an important regulator of clonal expansion.

Date: 2023
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DOI: 10.1038/s41467-023-38707-y

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