IMMUNOLOGY2026™ Conference Recordings For Attendees-Lag3-KIEELE domain plays a key role in Lag3-dependent Treg function

Video Transcription

Video Summary

The talk focused on how the intracellular KIELE motif of LAG-3 controls regulatory T cell (Treg) function. LAG-3 is an inhibitory receptor expressed on activated and exhausted T cells, and it is also highly expressed on FOXP3+ Tregs. The speaker’s lab previously showed that loss of LAG-3 disrupts Treg suppressive activity by shifting Tregs toward glycolysis and increasing MYC, LDHA, and PI3K signaling. Here, they generated Treg-specific mice lacking only the KIELE motif while keeping surface LAG-3 intact. These mice developed normal Treg homeostasis at rest, but during inflammation they showed worsened autoimmune encephalitis with more inflammatory CD4 T cells in the CNS. KIELE-deficient Tregs had elevated glycolysis and PI3K activity. Mechanistically, LAG-3 interacted with HPK1 and SLP-85, and loss of KIELE disrupted these interactions. HPK1 knockdown also impaired Treg suppression and increased glycolysis. Overall, the KIELE motif is essential for LAG-3-mediated Treg metabolic control and immune suppression.

Meta Tag

Date April 17, 2026 10:15 AM - 10:30 AM

Room 156

Session New Paradigms in T Cell Regulation

Speaker Booki Min

Track Immune Response Regulation: Cellular Mechanisms (IRC)

Year 2026

Keywords

LAG-3

KIELE motif

regulatory T cells

Treg metabolism

autoimmune encephalitis

April 17, 2026 10:15 AM - 10:30 AM

156

New Paradigms in T Cell Regulation

Booki Min

Immune Response Regulation: Cellular Mechanisms (IRC)

2026