Multiple neutralizing B-cell epitopes of human T-cell leukemia virus type 1 (HTLV-1) identified by human monoclonal antibodies. A basis for the design of an HTLV-1 peptide vaccine

Abstract

We have generated 153 human mAb reacting with natural envelope glycoprotein-gp46 of human T-cell leukemia virus type-1 (HTLV-1) by the EBV-transformation of B lymphocytes obtained from patients with HTLV-1-associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). Twenty-four of these mAb had neutralizing activity of HTLV-1 as determined by an HTLV-1-induced syncytium formation inhibition assay in vitro. The reactivity of these neutralizing mAb was studied by using 9 different synthetic peptides covering immunodominant regions of the gp46. Thirteen out of these 24 neutralizing mAb reacted with gp46 peptide 175-199, whereas one mAb reacted with gp46 213-236 and another one with gp46 288-317. The other 9 neutralizing mAb did not react with any of these peptides. Fine epitope mapping of the mAb reacting with gp46 peptide 175-199 revealed the presence of 4 distinct neutralizing B-cell epitopes on this region; (1)187-193, (2)191-196, (3)193-199, and (4) continuous conformational B-cell epitope. The competitive antibody-binding inhibition experiments by soluble phase synthetic peptides showed that the binding activity of these neutralizing mAb to the corresponding synthetic peptides is equal to or a little lower than that to native gp46 protein, suggesting that synthetic peptides can form structure very similar to the neutralizing epitopes on native gp46 protein. The present study is the first systematic demonstration of multiple neutralizing B-cell epitopes of HTLV-1 in human HTLV-1 infection. It would be possible to prepare a synthetic peptide vaccine against HTLV-1 based on these newly identified multiple linear neutralizing B-cell epitopes of HTLV-1.