Galectin-8 tandem-repeat structure is essential for T cell proliferation but not for co-stimulation.

CATTANEO V; TRIBULATTI MV; CAMPETELLA O

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Año: 2011 vol. 434 p. 153 - 160

0264-6021

Galectin-8 (Gal-8) is a tandem-repeat galectin containing N- and C-terminal carbohydrate recognition domains with differential glycan-binding specificity fused by a linker peptide. Gal-8 has two distinct effects on T CD4 cells: at high concentrations induces antigen-independent proliferation while at low concentrations co-stimulates antigen-specific responses. Associated Gal-8 structural requirements were dissected here. Recombinant homodimers N-N and C-C, but not single C- or N-domains, induced proliferation; however, single domains induced co-stimulation. These results point out that tandem-repeat structure was essential only for the proliferative effect, suggesting the involvement of lattice formation, while co-stimulation could be mediated by agonistic interactions. In both cases, C-C chimera displayed higher activity than Gal-8 indicating that the C-domain was mainly involved as was further supported by the strong inhibition of proliferation and co-stimulation in presence of blood group B antigen, specifically recognized by this domain. Classic galectin-inhibitors (lactose, thiodigalactoside) prevented proliferation but not co-stimulatory activity, which was inhibited by 3-O-β-D-Galactopyranosyl-D-arabinose. Interestingly, Gal-8 induced proliferation of naïve human T CD4 cells, varying from non- to high-responder individuals, while promoted cell death of phytohemagglutinin or CD3/CD28 pre-activated cells. Findings delineate the differential molecular requirements for Gal-8 activities on T cells, and disclose a dual activity relaying on activation state.