Influence of amino acid substitutions on antigenicity of immunodominant regions of the HTLV type I envelope surface gylcoprotein: a study using monoclonal antibodies raised against relevant peptides.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Influence of amino acid substitutions on antigenicity of immunodominant regions of the HTLV type I envelope surface gylcoprotein: a study using monoclonal antibodies raised against relevant peptides.

AIDS Res Hum Retroviruses. 1999 Jul 1;15(10):909-20. Unique Identifier : AIDSLINE MED/99335213
Londos-Gagliardi D; Jauvin V; Armengaut MH; Astier-Gin T; Goetz M; Huet S; Guillemain BJ; INSERM, U328, Structures et Fonctions des Retrovirus Humains,; Institute Bergonie, France.

Abstract: By the use of sera of human T cell leukemia virus type I (HTVL-I)-infected individuals it was shown that amino acid substitutions at positions 192 (proline to serine) and 250 (serine to proline) in major immunodominant regions (175-199 and 239-261) of the surface envelope glycoprotein (gp46) of the virus may influence the humoral response. Since human sera are polyclonal in nature, one cannot readily discriminate between an immunoglobulin-specific recognition and multiple bindings of diverse antibodies. To overcome this difficulty we generated murine monoclonal antibodies to synthetic peptides mimicking all or portions of these gp46 regions. The reactivity of some of these antibodies to synthetic peptides harboring (or not harboring) the preceding amino acid substitutions at position 192 or 250, to denatured gp46 by Western blotting, and to live (variously substituted) HTLV-I-infected cells, combined with blocking experiments with various peptides, allow us to conclude that the major epitopes (positions 183-191, 190-197, 190-199, and 246-252) in the two immunodominant regions may elicit different antibody responses according to their sequences. It is worth noting that in a reporter gene inhibition assay, it was found that a neutralizing monoclonal antibody (MF1), the epitope for which is located between residues 190 and 197, had a high level of activity when cells (2060) harboring a gp46 with proline at position 192 were used and had no activity toward cells (1010) with a serine at this position. Therefore our results establish that certain amino acid substitutions of gp46 may drastically affect the antigenicity of the molecule and the biological activity of the antibodies elicited.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Amino Acid Substitution Animal Antibodies, Monoclonal/BIOSYNTHESIS/IMMUNOLOGY Cell Line Cercopithecus aethiops Epitope Mapping Epitopes, B-Lymphocyte/*IMMUNOLOGY Fluorescent Antibody Technique, Indirect Gene Products, env/CHEMICAL SYNTHESIS/*IMMUNOLOGY Hamsters Human HTLV-BLV Antibodies/BIOSYNTHESIS/*IMMUNOLOGY HTLV-BLV Antigens/CHEMISTRY/*IMMUNOLOGY HTLV-I/*IMMUNOLOGY Immunoblotting Immunodominant Epitopes/CHEMISTRY/*IMMUNOLOGY Immunoglobulin Isotypes/IMMUNOLOGY Liver/CYTOLOGY/IMMUNOLOGY Mice Molecular Sequence Data Peptides/CHEMICAL SYNTHESIS/*IMMUNOLOGY Retroviridae Proteins, Oncogenic/CHEMICAL SYNTHESIS/*IMMUNOLOGY Support, Non-U.S. Gov't Vero Cells
991130
A99B1082

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .