IDENTIFICATION OF NOVEL NEUTRALIZATION-INDUCING REGIONS OF THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I ENVELOPE GLYCOPROTEINS WITH HUMAN HTLV-I-SEROPOSITIVE SERA

The humoral immune response in sera from 30 human T cell lymphotropic virus type I (HTLV-I)-positive individuals from Martinique in the Fren ch West Indies was studied. The subjects were subdivided into those su ffering from TSP/HAM and those being asymptomatic. In general, TSP/HAM patient sera seemed to contain more virus-specific antibodies than di d the sera from the asymptomatic subjects. Three of the 13 TSP/HAM ser a and 1 of the 17 asymptomatic sera contained HTLV-I-specific IgM anti bodies, whereas 6 and 5 sera, respectively, contained IgA antibodies. By correlating the ability of patient sera to inhibit HTLV-I-induced s yncytia with their antibody reactivity in ELISA to 42 synthetic peptid es, together corresponding to the entire envelope glycoprotein of HTLV -I, a number of putative neutralizing domains were identified. Eight s ynthetic peptides representing the regions with the highest coefficien t of correlation between neutralizing titer and ELISA reactivity were employed to specifically adsorb potentially neutralizing antibodies, a nd were also used directly, without sera, in the syncytium-neutralizin g test. By those techniques, three novel and two previously described domains that seemed to contain neutralizing epitopes were identified. Two of the novel neutralizing sites resided in the external glycoprote in (gp46) and were contained within amino acids 53-75 and 287-311, res pectively, and one was located in the transmembrane glycoprotein (gp21 ) within amino acids 346-368. Our findings may have implications for t he rational design of subunit vaccines for prevention of and/or altera tion of the clinical outcome of HTLV-I-related diseases.