Galectin-1 induces partial TCR zeta-chain phosphorylation and antagonizes processive TCR signal transduction

Galectin-1 is an endogenous lectin with known T cell immunoregulatory activ ity, though the molecular basis by which galectin-1 influences Ag specific T cell responses has not been elucidated. Here, we characterize the ability of galectin-1 to modulate TCR signals and responses by T cells with well d efined hierarchies of threshold requirements for signaling distinct functio nal responses. We demonstrate that galectin-1 antagonizes TCR responses kno wn to require costimulation and processive protein tyrosine phosphorylation , such as IL-2 production, but is permissive for TCR responses that only re quire partial TCR signals, such as IFN-gamma production, CD69 up-regulation , and apoptosis, Galectin-1 binding alone or together with Ag stimulation i nduces partial phosphorylation of TCR-zeta and the generation of inhibitory pp21 zeta, Galectin-1 antagonizes Ag induced signals and TCR/costimulator dependent lipid raft clustering at the TCR contact site. We propose that ga lectin-1 functions as a T cell "counterstimulator'' to limit required prote in segregation and lipid raft reorganization at the TCR contact site and, t hus, processive and sustained TCR signal transduction, These findings suppo rt the concept that TCR antagonism can arise from the generation of an inhi bitory pp21 zeta-based TCR signaling complex. Moreover, they demonstrate th at TCR antagonism can result from T cell interactions with a ligand other t han peptide/MHC.