MAPPING THE LECTIN-LIKE ACTIVITY OF TUMOR-NECROSIS-FACTOR

Tumor necrosis factor (TNF), but not lymphotoxin (LT), is directly try panolytic for salivarian trypanosomes. This activity was not blocked b y soluble 55-kilodalton and 75-kilodalton TNF receptors, but was poten tly inhibited by N,N'-diacetylchitobiose, an oligosaccharide that bind s TNF. Comparative sequence analysis of TNF and LT localized the trypa nocidal region, and synthetic peptides were trypanolytic. TNF molecule s in which the trypanocidal region was mutated or deleted retained tum oricidal activity. Thus, trypanosome-TNF interactions occur via a TNF domain, probably with lectin-like affinity, which is functionally and spatially distinct from the mammalian TNF receptor binding sites.