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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Trends Immunol. 2021 Feb 1;42(3):261–272. doi: 10.1016/j.it.2021.01.004

Figure 1. Approaches to preventing GvHD mediated by OTS T cells.

Figure 1.

Top: TCRs of unmodified OTS alloreactive T cells are translated, assembled, transported to cell surface, recognize mismatched recipients’ healthy tissues, initiate downstream signaling and release effector molecules, such as cytolytic enzymes and inflammatory cytokines, leading to tissue damage. This can be prevented by removing functional TCRs from cell surface through ① knocking out one or two genes encoding components of the TCR complex, ② trapping TCR in the endoplasmic reticulum (ER) through anti-CD3ε PEBLs, or ③ preventing alloreactive TCR signaling by expressing TIM, a dominant-negative form of CD3ζ. Bottom: An alternative direction is to selectively expand non-alloreactive immune effectors to include in the final product.