A CD25-chemokine receptor complex initiates noncanonical IL-2 signaling.

ABSTRACT: An antimouse CD25 antibody, PC61, induces a complex formed by the interleukin-2 (IL-2)-dependent association of CD25 with CCR7 and an alternative IL-2 signaling pathway that results in integrin activation in CD4⁺CD25^HiFoxp3⁺ regulatory T cells (Tregs). Here, we used structure-based design together with combinatorial screening to identify a human IL-2 mutant (IL-2(E52K)) that disrupts CD25-CCR7 complex formation while retaining the full CD25 affinity of the parent molecule. An anti-human CD25 (hCD25), 7G7B6, drove formation of IL-2-dependent hCD25-CCR7, CD25-CXCR4, and CD25-CCR5 complexes and induced integrin activation in hCD25-expressing IL-2Rα⁺ YT-1 cells, Jurkat T cells, and primary Tregs. IL-2(E52K) failed to support activation in CCR5^Lo

SUBMITTER: Lee HS 

PROVIDER: S-EPMC12810549 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature