Mapping antigenic sites on the major outer membrane protein of Chlamydia trachomatis with synthetic peptides

Zhong, Guangming; Reid, Ronald E.; Brunham, Robert C.

doi:10.1128/iai.58.5.1450-1455.1990

Cited by 48 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This MAb was reactive with two overlapping peptides from the VD IV region, which was reported by others to contain neutralizing epitopes (2,20). Thus, this region contains a species-specific epitope (TLNPTI) that is surface exposed on serovars A, D, E, F, K, L2, and L3 but not on serovars B, C, H, and 1 (43). Our MAb strongly neutralized both serovar D (B serogroup) and serovar K (intermediate serogroup) but failed to neutralize serovar L2 (B serogroup) in a complement-independent neutralization assay.…”

Section: Resultsmentioning

confidence: 86%

Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies

et al. 1994

View full text Add to dashboard Cite

The major outer membrane protein (MOMP) is a primary target antigen for the development of chlamydial vaccine. This protein is composed of four variable domains (I to IV) flanked by constant regions. Some of the variable domains contain antigenic determinants that elicit a neutralizing antibody response. Murine monoclonal antibodies (MAbs) against three nonoverlapping epitopes of MOMP were developed. One of these, called DP1O, bound to all serovars, as shown by immunoblot analysis, and neutralized chlamydial infectivity for hamster kidney (HaK) cells in a complement-independent in vitro assay. Furthermore, analysis of the fine specificity of this MAb showed that it recognized a synthetic peptide contained within variable domain IV of the MOMP. Anti-idiotypic antibodies (aId) directed against this anti-MOMP MAb were produced in rabbits. These aId specifically bound to the relevant idiotype (DP10) and inhibited the binding of anti-MOMP MAb (DP10) to MOMP preparations in a dose-dependent fashion. The specificity of our aId for the binding site of anti-MOMP MAb is further suggested by the binding inhibition of affinity-purified aId to DP1O by the synthetic peptide defined by the idiotype. In addition, these aId also reacted with anti-MOMP antisera from rats and mice, suggesting an idiotypic cross-reactivity between these species. Finally, immunization of naive mice with aId induced an antibody response directed against the peptide defined by our anti-MOMP MAb and with neutralizing activity. Taken together, these data suggest that aId mimic a neutralization site on MOMP and could serve as a surrogate antigen to induce protective immunity against Chlamydia trachomatis.

show abstract

Section: Resultsmentioning

confidence: 86%

Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Within the C. trachomatis species, related serovars share a common subspecies-specific epitope, which is located in a surface-exposed region of VS IY Monoclonal antibodies to these surface-exposed epitopes neutralise C. trachomatis infection in vitro for cell culture, and in vivo in the primate eye model (195). These protective B-cell epitopes have been defined to single amino acid resolution using the Pepscan@ procedure (33,196,197,199). Within a genovar, variants arise stepwise as a result of single base mutation.…”

Section: Neutralising Antibody and Antigenic Variationmentioning

confidence: 99%

The immunobiology and immunopathology of chlamydial infections

Ward

1995

APMIS

171

125

View full text Add to dashboard Cite

Chlamydiae are obligate intracellular bacterial pathogens of eukaryotic cells responsible for a wide variety of important human and animal infections. In humans, chlamydial infections are generally localised to superficial epithelial or mucosal surfaces, are frequently asymptomatic and may persist for long periods of time if untreated, inducing little protective immunity. Nevertheless, neutralising antibodies of limited efficacy are produced against the main chlamydial outer envelope protein, while gamma interferon (IFNγ) is chlamydiastatic and paradoxically may play a role both in chlamydial persistence and in protective immunity. Delayed hypersensitivity responses to chlamydiae caused by repeated or persistent infection are thought to be important in the development of the severe scarring sequelae characteristic of cicatricial trachoma and of chronic salpingitis. Chlamydial heat shock proteins bearing close homology with their human equivalents may be major targets for immunopathological responses and their expression is upregulated in IFNγ induced persistent infection. C. pneumoniae, a common cause of acute respiratory infection in humans, may persist in coronary arteries and is strongly implicated as a risk factor in atherosclerosis and in acute myocardial infarction. This paper reviews the immunology and immunopathology of chlamydial infections in the context of the unique biology of this fascinating but challenging group of organisms.

show abstract

“…C. trachomatis serovars B (TW5/OT) and C(TW3/OT) were used. Organisms were grown in HeLa 229 cell monolayers, and the purified EBs were prepared as previously described (28).…”

Section: Methodsmentioning

confidence: 99%

Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked

Zhong

Brunham

1992

Infect Immun

Self Cite

View full text Add to dashboard Cite

The effects of both H-2 and non-H-2 genes on antibody responses to two Chlamydia trachomatis heat shock proteins (hsp60 and hsp70) were investigated. These chlamydial proteins are homologs of Escherichia coli GroEL (hsp60) and DnaK (hsp70) and are highly sequence conserved between bacterial and mammalian sources. Antibody responses among 17 different strains of mice immunized with C. trachomatis serovar B and serovar C elementary bodies were evaluated by immunoblot, radioimmunoprecipitation and enzyme-linked immunosorbent assay. Antibody responses to the two proteins displayed host genetic restriction. Of six distinctive H-2 haplotypes, only H-2d generated high antibody responses to hsp70. Five of the six H-2 haplotypes, i.e., H-2a, H-2d, H-2k, H-2q, and H-2s, produced high antibody responses to hsp60. Only the H-2b-bearing strain had low antibody responses to hsp60. By using congenic and H-2 recombinant strains, the genes responsible for regulating antibody responses to hsp70 and hsp60 were mapped to the K-IA region of the H-2 locus. In F1 hybrid crosses between high and low responders, high responses to hsp60 and hsp70 were dominant traits. Other genes outside the H-2 locus also influenced antibody responses to hsp60 and hsp70, since inbred strains of identical H-2 but different background genes displayed variable antibody responses to the proteins. The genetic control of murine immune responses to C. trachomatis hsp60, a putative chlamydial immunopathologic antigen, suggests that a similar genetic mechanism may also exist in humans, and this observation may help to explain the observed variability in the spectrum of chlamydial diseases seen in humans.

show abstract

Mapping antigenic sites on the major outer membrane protein of Chlamydia trachomatis with synthetic peptides

Cited by 48 publications

References 33 publications

Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies

Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies

The immunobiology and immunopathology of chlamydial infections

Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked

Contact Info

Product

Resources

About