Fig. 4

Antigenicity analysis and linear alignment of the shared peptide on Fas and gp120. (A) Measurement of antigenicity of VEINCTR-N region within 50 amino acid (a.a.) length domains of both Fas and gp120 by the Antheprot method. The computer analysis assigned high antigenicity to a 12 a.a. epitope of Fas, including the intact sequence in contiguity with Leu 113 and Glu 114 of peptide #1. By contrast, similar values of high antigenicity were attributed only in part to the shared epitope on the gp120 domain, since Val 171, Glu 172, and Ile 173 were not antigenic. (B) Linear alignment of a portion of the first consensus sequence of tumor necrosis factor (TNF) type I receptor and Fas incorporating 5 Cys residues in both receptors. Hyphens (-) are introduced to obtain maximal homology. VEINCTR-N was present within the consensus sequence and showed high homology with its parallel domain on tumor necrosis factor-α receptor (TNFα-R). Shaded areas indicate full identity of a.a. residues; whereas, the similarity of charge is depicted by vertical links. The homology between both stretches was calculated as 42.4% of identity and 60.6% of similarity. Putative glycosylation site is indicated by an asterisk on Asn 118 of VEINCTR-N. The arrows indicate several residues within the consensus sequence of Fas, which are considered relevant for ligand binding to the receptor (39). (C) Three-dimensional molecular model of VEINCTR-N on both Fas and gp120. The conformation related to Fas was obtained by computer evaluation of the high homology with the consensus sequence of TNFα-R. The model also includes the Cys residues (yellow) in identical posi-tion, as assembled in disulphide bonds on TNFα-R. This suggests that Cys 119 included within VEINCTR-N is joined to Cys 104 and that the presence of another disulphide link (Cys 107 = Cys 127) in the conformed structure could be critical for antigenicity. Conversely, Cys 175 of gp120 epitope is isolatedly expressed with no involvement in disulphide bonds (carbon atoms are in gray, nitrogen in blue, and oxygen in red, orientation is in green).