Immune synapse molecules knockout in induced pluripotent stem cells enables broad NK cell resistance in T cell progeny.

ABSTRACT:

Introduction

Allogeneic iPSCs provide a potential source for regenerative T cell therapies, yet their clinical application remains limited by immune rejection driven by human leukocyte antigen (HLA) incompatibility. Knockout of β2-microglobulin (B2M) eliminates HLA class I expression and protects against CD8⁺ T cell-mediated killing, but paradoxically provokes natural killer (NK) cell activation via the "missing-self" response. Existing approaches seek to enhance inhibitory signaling or dampen activating signals, yet these approaches achieve only partial NK evasion due to the extraordinary heterogeneity of NK receptor repertoires.

Methods

We developed a broader and more universal immune evasion strategy by targeting immune synapse (IS) adhesion molecules that crit

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12828601 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature