Reactivity of AIDS patient sera with a peptide derived from HIV type 1NY5 glycoprotein 120 V3 loop and consensus sequence of collagens.

Previously we have reported the structural similarity between a portion of HIV-1 envelope glycoprotein (gp 120) and human immunoglobulin heavy chain variable region (IgVh) of group HI gene products.1-3 The similarity was detected on a continual fragment of consensus sequences involving about 42 residues. This represents the first reported gpl20/lg homology that includes a hypervariable gpl20 portion, i.e., the V3 loop also denoted as the principal neutralizing determinant (PND).4 That observation led us to suggest that gpl20 or V3 loop fragments might play a role in triggering autoimmune responses5 being thus inadequate for vaccine development.6 The immunogenic determinant of the virus envelope could initiate the formation of antibodies or effector lymphocytes, which, in turn, might react with homologous host protein sequences. Since similarity of diverse V3 loops with the portion of Vh III molecules was confirmed by several criteria,3-6 and since the V3 loop is one of the most variable gpl20 regions, we suggested that the V3 loop may both share linear epitopes with host proteins and interact with the complementary determinants of antigen receptors.5,6 Here, we report the sequence homology between a V3 loop region of HIV-1 strain New York 5 (HIV-l,^) and several human collagens, particularly collagen type VI cd chain (Fig. la), obtained by a computer-assisted search7 of protein sequence database Swiss-Prot 25.8 To answer the question of whether this level of sequence similarity is sufficient for immunological cross-reactivity between the selected peptides, an HTV-Inyj gpl20 V3 loop-derived peptide KKGIAIGPGRTLY and peptide CKGCAGDPGRPDD, which encompasses the consensus KG**G*PGR of homologous collagen sequences (Fig. lb), were designed and synthesized. In the later peptide, each amino acid