Localization of epitopes of herpes simplex virus type 1 glycoprotein D

Abstract

We previously defined eight groups of monoclonal antibodies which react with distinct epitopes of herpes simplex virus glycoprotein D (gD). One of these, group VII antibody, was shown to react with a type-common continuous epitope within residues 11 to 19 of the mature glycoprotein (residues 36 to 44 of the predicted sequence of gD). In the current investigation, we have localized the sites of binding of two additional antibody groups which recognize continuous epitopes of gD. The use of truncated forms of gD as well as computer predictions of secondary structure and hydrophilicity were instrumental in locating these epitopes and choosing synthetic peptides to mimic their reactivity. Group II antibodies, which are type common, react with an epitope within residues 268 to 287 of the mature glycoprotein (residues 293 to 312 of the predicted sequence). Group V antibodies, which are gD-l specific, react with an epitope within residues 340 to 356 of the mature protein (residues 365 to 381 of the predicted sequence). Four additional groups of monoclonal antibodies appear to react with discontinuous epitopes of gD-1, since the reactivity of these antibodies was lost when the glycoprotein was denatured by reduction and alkylation. Truncated forms of gD were used to localize these four epitopes to the first 260 amino acids of the mature protein. Competition experiments were used to assess the relative positions of binding of various pairs of monoclonal antibodies. In several cases, when one antibody was bound, there was no interference with the binding of an antibody from another group, indicating that the epitopes were distinct. However, in other cases, there was competition, indicating that these epitopes might share some common amino acids.

Antibody-Induced Conformational Changes in Herpes Simplex Virus Glycoprotein gD Reveal New Targets for Virus Neutralization

“…It was previously noted that antibodies to two distinct epitopes on gD can behave synergistically, but in that experiment, both antibodies blocked receptor binding, i.e., H170 (group VII) blocked binding of HVEM and H128 (group 1b) blocked both. We know from earlier studies that group VII and 1b MAbs do not compete with each other (11,13,17,36). Here, we found an enhancing effect on both the extent and rate of neutralization by combining the neutralizing MAb MC2 with a nonneutralizing MAb such as MC4, MC10, or MC14.…”

Mapping of a region of dengue virus type-2 glycoprotein required for binding by a neutralizing monoclonal antibody

“…Similar differences have been observed by others. For example, Eisenberg et al (1985) identified an antigenic site in the aa 268-287 sequence of glycoprotein [ _ plaques with immune serum -] Mean percent plaque reduction calculated from the average of duplicate titration as ,_ 1 pl~it~n~m]…”

A Salmonella typhimurium htrA live vaccine expressing multiple copies of a peptide comprising amino acids 8–23 of herpes simplex virus glycoprotein D as a genetic fusion to tetanus toxin fragment C protects mice from herpes simplex virus infection

“…The peptide comprising amino acids (aa) 8-23 of the amino-terminus of gD contains the dominant T cell epitope (Heber-Katz et al, 1985;Wyckoff et al, 1988) and also the continuous, type common B cell epitope comprising 11-19 aa (Eisenberg et al, 1985b). A monoclonal antibody that recognises the 11-19 aa epitope neutralised the virus in vitro (Minson et al, 1986).…”