Mapping of linear antigenic determinants on glycoprotein C of herpes simplex virus type 1 and type 2 recognized by human serum immunoglobulin G antibodies

Abstract

Using membrane-based dekapeptides, the reactivity of human serum antibodies with linear antigenic determinants of herpes simplex virus (HSV) type 1 and type 2 glycoprotein C (gC-1, gC-2) was studied by pep scan and immunodot assay. The entire coding sequences of gC-1 and gC-2 were screened for the presence of linear epitopes by pep scan. Peptides recognized in an HSV-1 type-specific manner were mainly identified within the N-terminal third and at the C-terminus of gC-1, whereas most type-common antibodies were directed against colinear peptides within the central parts of gC-1 and gC-2. The type-specific reaction of human sera with gC-2 peptides in pep scan was poor. Eight peptides identified as immunoreactive by pep scan were further tested in immunodot assay for their reactivity with a human serum panel. None of the eight HSV-negative sera gave positive results by immunodot assay. Positive reactions with gC peptides were found to be strongly age-dependent, i.e., the rate of positive reactions was significantly higher in HSV-positive adults than in HSV-positive children. Antibody reactivity with two type-common gC peptides was demonstrated in 17 out of 28 HSV-positive sera. A putative type-specific gC-2 peptide employed in immunodot assay was inconsistently recognized by human sera. Twenty HSV-positive sera reacted with at least 1 of 5 type-specific gC-1 peptides. Nine sera showing no reactivity with glycoprotein G of HSV-1 (gG-1) by immunobloting recognized type-specific gC-1 peptides in immunodot assay. Thus, gC-1 peptides might allow the detection of HSV-1-specific antibodies in individuals showing no reactivity with commonly employed HSV-1-specific diagnostic antigenes, i.e., purified or recombinant gG-1.

Prediction and Identification of Potential Immunodominant Epitopes in Glycoproteins B, C, E, G, and I of Herpes Simplex Virus Type 2

“…The epitope (210–230 aa) of gC2 was reported to be the immunodominant epitope [23], which is consistent with the prediction in the current study. However, the epitope (216–223 aa) of gC2 was selected in the current study because it had higher antigenicity than the epitope (126–132 aa) of gC2, as shown in the EIA results.…”

Linear Multiepitope (Glyco)peptides for Type-Specific Serology of Herpes Simplex Virus (HSV) Infections

“…The situation is different for the gC2 peptides: Peptides 11, 12, and 13 reacted with 15 of 16 HSV-2­(+) sera and have very little homology with the corresponding type 1 protein. Both peptides 11 ( 41 ASN­AAP­SAS­PRN­ASA­PRT­TP 60 ), which covers the previously reported epitope gC2 43–52 , and 13 ( 60 TPP­QPR­KAT­KSK­AST­AKP­AP 79 ) also showed some weak reactivity toward a few HSV-1­(+) (Figure ) and negative sera (data not shown), whereas peptide 12 ( 50 RNA­SAP­RTT­PTP­PQP­RKA­TK 69 ) was the most type-specific one and therefore selected for further analysis.…”

Glycoprotein G of herpes simplex virus type 1: identification of type-specific epitopes by human antibodies

“…The reason for the retained type-specificity in regions with high similarity might depend on the existence of type-specific amino acids with key functions in antibody binding. As an example, some linear peptides derived from homologous parts of gC were recently shown to be presented in a type-specific manner (Ackermann et al , 1998 ). The importance of key residues has previously been shown in the work of Dolter et al (1992) for mouse MAb reactivity to HSV gC-1.…”