URTICA-DIOICA AGGLUTININ - A SUPERANTIGENIC LECTIN FROM STINGING NETTLE RHIZOME

Urtica dioica agglutinin (UDA) is an unusual plant lectin that differs from all other known plant lectins with respect to its molecular stru cture and its extremely low specific agglutination activity. We recent ly reported that this small lectin (8.5 kDa) is a T cell mitogen disti nguishable from classical T cell lectin mitogens by its ability to dis criminate a particular population of CD4+ and CD8+ T cells as well as its capacity to induce an original pattern of T cell activation and cy tokine production. The mechanism by which UDA activates T cells was in vestigated and compared with the conventional T cell mitogen Con A and the known superantigen staphylococcal enterotoxin B. Our data show th at T cell proliferation induced by UDA is strictly dependent on AC exp ressing MHC class II molecules but is not MHC restricted. This prolife ration can be partially inhibited by anti-I-A or anti-I-E mAb and comp letely blocked by a mAb recognizing monomorphic determinants on the la molecule. UDA indeed binds to specific carbohydrate structures presen t on class II molecules. UDA-induced T cell stimulation is dependent o n TCR recognition of the unprocessed intact molecule in association wi th various Ia molecules. T cell response to UDA is clonally expressed and correlates with particular TCR Vbeta gene families usage. This sti mulation leads to a sixfold enrichment of Vbeta8.3+ T cells within 3 d ays. Therefore, UDA appears to use the same molecular mechanism as str ucturally unrelated bacterial or retroviral superantigens and we propo se that this lectin is a superantigen. UDA, which is not a pathogenici ty factor, could provide a useful probe for the analysis of T cell act ivation by superantigens.