Continuous epitopes of human lymphotoxin and their topographies

Human lymphotoxin (hLT or TNF-beta) is a lymphokine that is structurally and functionally related to tumor necrosis factor alpha (TNF-alpha). The continuous epitopes of hLT were located by examining the cross-reaction between rabbit anti-hLT antibody and peptides derived from proteolytic digestion and chemical synthesis. Three antigenic sites, corresponding to residues 40-48, 83-94 and 139-147, of the protein sequence, were located by this approach. Since residues 49-57 also exhibited trace antigenicity, but residues 45-52 displayed no reaction, the whole peptide fragment consisting of residues 40-57 might be necessary for antigenicity. A comparison of the antigenic determinants with the loop structures obtained from X-ray crystallographic studies of hLT showed that all of the epitopes are found on or adjacent to functionally important domains.