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

Eishi Baba, M. Nakamura, Y. Tanaka, M. Kuroki, Y. Itoyama, S. Nakano, Y. Niho

研究成果: ジャーナルへの寄稿記事

47 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1013-1024
ページ数12
ジャーナルJournal of Immunology
151
発行部数2
出版物ステータス出版済み - 1 1 1993

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Deltaretrovirus
B-Lymphocyte Epitopes
Subunit Vaccines
Monoclonal Antibodies
Peptides
Tropical Spastic Paraparesis
Epitope Mapping
Immunodominant Epitopes
Synthetic Vaccines
Competitive Binding
Spinal Cord Diseases
Virus Diseases
Giant Cells
Human Herpesvirus 4
Epitopes
Glycoproteins
Proteins
B-Lymphocytes
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology

これを引用

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. / Baba, Eishi; Nakamura, M.; Tanaka, Y.; Kuroki, M.; Itoyama, Y.; Nakano, S.; Niho, Y.

:: Journal of Immunology, 巻 151, 番号 2, 01.01.1993, p. 1013-1024.

研究成果: ジャーナルへの寄稿記事

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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.",
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