Epitope mapping of human monoclonal antibodies recognizing conformational epitopes within HTLV type 1 gp46, employing HTLV type 1/2 envelope chimeras

AIDS Res Hum Retroviruses. 2002 Jan 1;18(1):57-70. doi: 10.1089/088922202753394727.

Abstract

The majority of the antibody response to HTLV-1 surface glycoprotein, gp46, is directed at conformational epitopes. However, the regions of HTLV-1 gp46 that contain conformational epitopes are poorly defined. We previously reported on human monoclonal antibodies (hMAbs) to conformational epitopes within the HTLV-1 surface glycoprotein (gp46) that inhibit HTLV-1-mediated syncytium formation (Hadlock KG, Rowe J, Perkins S, et al.: J Virol 1997;71:5828-5840). To localize the conformational epitopes recognized by these antibodies, chimeric envelope proteins were constructed in which selected regions of the HTLV-1 envelope were replaced with the corresponding sequences from other members of the HTLV family of retroviruses. The chimeras were tested for reactivity with three hMAbs to conformational epitopes in HTLV-1 gp46, PRH-7A, PRH-3, and PRH-4, and one hMAb to a linear epitope, 0.5alpha. hMAb PRH-3 was specifically nonreactive with a chimera that replaced amino acids 32-36 of HTLV-1 gp46 and exhibited sharply reduced reactivity with a chimera that replaced amino acids 224-251 of HTLV-1 with the corresponding HTLV-2 sequence. hMAb PRH-4 was specifically nonreactive with a construct replacing amino acids 1-162 of HTLV-1 gp46 with the corresponding HTLV-2 sequence. Thus, HTLV-1 gp46 contains multiple conformational epitopes located in the amino-terminal portion of the protein.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Viral / immunology*
  • Epitope Mapping
  • Flow Cytometry
  • Gene Products, env / genetics
  • Gene Products, env / immunology*
  • Human T-lymphotropic virus 1 / immunology*
  • Human T-lymphotropic virus 2 / genetics
  • Human T-lymphotropic virus 2 / immunology*
  • Humans
  • Jurkat Cells
  • Molecular Sequence Data
  • Precipitin Tests
  • Recombination, Genetic
  • Retroviridae Proteins, Oncogenic / genetics
  • Retroviridae Proteins, Oncogenic / immunology*
  • Sequence Alignment

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Gene Products, env
  • Retroviridae Proteins, Oncogenic
  • gp46 protein, Human T-cell leukemia virus type I