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

Zhong, Guangming; Brunham, Robert C.

doi:10.1128/iai.60.8.3143-3149.1992

Cited by 68 publications

(21 citation statements)

References 25 publications

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“…Our results represent the first study of HLA class II restriction and several measures of cellular immunity to both whole and recombinant chlamydial antigens in a community in which exposure to C. trachomatis is endemic. In the mouse, antibody responses to both hsp60 and hsp70 have been shown to be H-2-linked [27]. Furthermore, the mortality rate following mouse pneumonitis agent infection has been shown to be strain-dependent [28] and this correlated with reciprocal Th1/Th2 immune responses in different strains.…”

Section: Discussionmentioning

confidence: 99%

T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring

Holland

Bailey

Conway

et al. 1996

Clinical and Experimental Immunology

129

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SUMMARYIncreased stimulation of Th2 cytokines may contribute to the development of persistent ocular chlamydial infection, resulting in the blinding pathological changes of trachoma. Proliferation and cytokine production profiles of PBMC in response to stimulation with antigens of Chlamydia trachomatis were compared in 30 patients with severe conjunctival scarring due to trachoma and in 30 age-, sex-and location-matched controls. Interferon-gamma (IFN-°) and IL-4 were detected at the single-cell level by ELISPOT assay. Transcription of the genes encoding IFN-°, IL-4 and IL-10 was detected in mRNA isolated from parallel cultures of PBMC using reverse transcriptase-polymerase chain reaction (RT-PCR). Incubation with the chlamydial heat shock protein (hsp)60 resulted in increased numbers of IL-4-producing cells in PBMC isolated from patients with scarring disease and increased secretion of IFN-°from PBMC of control subjects. Incubation with the chlamydial major outer membrane protein (MOMP) increased the number of IFN-°-producing cells in the control group only. Messenger RNA encoding IL-4 was only detected in PBMC of patients with scarring disease after in vitro stimulation with chlamydial antigens, but IFN-°mRNA and IL-10 mRNA were also more frequently detected in this group. Thirty-eight subjects were HLA-DRB1 and -DQB1 typed. Associations were observed between certain HLA class II alleles and cellular immune responses to chlamydial antigens. No HLA associations were found with clinical status, and overall we found no evidence of strong associations and the type of immune response. These data are consistent with a role for Th2 cells and cytokines in the pathogenesis of trachomatous scarring.

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Section: Discussionmentioning

confidence: 99%

T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring

Holland

Bailey

Conway

et al. 1996

Clinical and Experimental Immunology

129

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“…Our findings regarding the MHC linkage of the MOMPspecific antibody response and the failure of intermolecular T-cell help in low-MOMP-responder mouse strains raise issues that are of fundamental importance to the design of an optimal Chlamydia subunit vaccine. Although an MHC linkage for the antibody response to the C. trachomatis Hsp6O and Hsp7O proteins has been reported (41), an influence of MHC on the antibody response to MOMP was not detected for the one C. trachomatis serovar in which this issue has been quantitatively analyzed (33). Given the fine-specificity differences in the immunodominant variable regions of the 15 known C. trachomatis serovars, this does not permit any broader generalization.…”

Section: Infect Immunmentioning

confidence: 95%

“…Other evidence, however, suggests that the immune response to various chlamydial components is under the influence of H-2-linked genes. Zhong and Brunham have reported that the antibody responses to C. trachomatis heat shock proteins Hsp6O and Hsp7O are MHC linked (41). This may be impor-tant, since it has been suggested that the 57-kDa protein (the Hsp6O homolog) plays a role in eliciting the immunopathologies which are a decisive factor in chlamydial disease manifestations (25,26).…”

mentioning

confidence: 99%

Dissociation of immune determinants of outer membrane proteins of Chlamydia psittaci strain guinea pig inclusion conjunctivitis

et al. 1994

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Chlamydia trachomatis is an important human pathogen. Research to develop a Chlamydia vaccine has focused on the major outer membrane protein (MOMP). Determinants of this protein elicit serovar-specific neutralizing antibodies which are thought to play a critical role in protective immunity. MOMP-specific antibody responses are highly variable in the polymorphic population. Genetic factors which might influence the MOMP-specific immune response are consequently of particular interest. The C. psittaci strain guinea pig inclusion conjunctivitis (GPIC) is a natural pathogen of the guinea pig that causes both ocular and genital tract infections that closely resemble those caused by C. trachomatis in humans. As such, it provides an excellent model for disease. In this report, we explore the influence of major histocompatibility complex-linked genes on the MOMP-specific antibody response in mice immunized with either whole GPIC elementary bodies or recombinant GPIC MOMP. Our results indicate that the MOMP-specific antibody response is major histocompatibility complex linked such that mice of the H-2d haplotype are high responders while mice of the H-2 haplotype are low responders. We demonstrate that MOMP-specific B cells are present in H-2k strains which are, however, deficient in MOMP-specific helper T cells. Although immunization of low-MOMPresponder strains with whole chlamydial elementary bodies induces high levels of immunoglobulin G antibody specific for Omp2, the cysteine-rich outer membrane protein, MOMP-specific B cells are unable to receive help from Omp2-specific T cells. The failure of intermolecular help from Omp2-specific T cells and related observations raise important issues regarding the processing and presentation of chlamydial antigens and the design of optimal subunit vaccines.

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“…Other chlamydial antigens which may be involved in adhesion of the organisms to the host cell include the 58-60 kDa omp2 EB outer envelope protein (1 69), the 18 and 28 kDa histonelike proteins (175) and a chlamydial heat shock protein analogous to human hsp-70 (137,198). It has been suggested that S-S cross-linked polymers of omp2 in the periplasmic space of the EB form an S-S linked network, with the periplasmic domain of the cytoplasmic membrane-embedded small cysteine-rich lipoprotein omp3 and perhaps other membrane proteins (41).…”

Section: Attachmentmentioning

confidence: 99%

The immunobiology and immunopathology of chlamydial infections

Ward

1995

APMIS

171

125

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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.

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

Cited by 68 publications

References 25 publications

T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring

T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring

Dissociation of immune determinants of outer membrane proteins of Chlamydia psittaci strain guinea pig inclusion conjunctivitis

The immunobiology and immunopathology of chlamydial infections

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