Recessive expression of the H2A‐controlled immune response phenotype depends critically on antigen dose

Barcenas-Morales, Gabriela; Merkenschlager, Matthias; Wahid, Faisal; Döffinger, Rainer; Iványi, Juraj

doi:10.1046/j.1365-2567.2000.00956.x

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…Competition ELISA showed that whereas an IgG anti-Acr mAb (TBG65) inhibited binding of TBA61 to Acr-coated plates, 2E9IgA1 did not (data not shown). Moreover, 2E9IgA1 and TBA61 bound to different, partly overlapping, truncated Acr recombinants, and neither bound linear peptides of Acr (28) (data not shown). We conclude that 2E9IgA1 and TBA61 recognize different (yet structurally undefined) epitopes on Acr.…”

Section: Resultsmentioning

confidence: 94%

A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

Balu

Reljić

Lewis

et al. 2011

The Journal of Immunology

162

154

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Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the mycobacterial α-crystallin Ag and for the human FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-γ significantly inhibited pulmonary H37Rv infection in mice transgenic for human CD89 but not in CD89-negative littermate controls, suggesting that binding to CD89 was necessary for the IgA-imparted passive protection. 2E9IgA1 added to human whole-blood or monocyte cultures inhibited luciferase-tagged H37Rv infection although not for all tested blood donors. Inhibition by 2E9IgA1 was synergistic with human rIFN-γ in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of FcαRI (CD89) for human IgA-mediated protection is important for understanding of the mechanisms involved and also for translation of this approach toward development of passive immunotherapy of tuberculosis.

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Section: Resultsmentioning

confidence: 94%

A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

Balu

Reljić

Lewis

et al. 2011

The Journal of Immunology

162

154

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“…Though this model of selective multibacillary lung disease seems relevant, the antigen specificity of the underlying immune responses was not identified. Although antibody responses to different antigens and epitopes is under H-2A control following immunization with soluble antigens in adjuvants ( 84 , 85 ), there is no clear corresponding evidence following Mtb infection. On the other hand, antibody responses to hsp65 and hsp71 antigens ( 86 ) and liver granuloma formation ( 87 ) following Mtb infection were associated with non-H-2 genes.…”

Section: Association Of Hla-dr and Antibody Epitope Specificity With mentioning

confidence: 99%

Function and Potentials of M. tuberculosis Epitopes

Iványi

2014

Front. Immunol.

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Study of the function of epitopes of Mycobacterium tuberculosis antigens contributed significantly toward better understanding of the immunopathogenesis and to efforts for improving infection and disease control. Characterization of genetically permissively presented immunodominant epitopes has implications for the evolution of the host–parasite relationship, development of immunodiagnostic tests, and subunit prophylactic vaccines. Knowledge of the determinants of cross-sensitization, relevant to other pathogenic or environmental mycobacteria and to host constituents has advanced. Epitope-defined IFNγ assay kits became established for the specific detection of infection with tubercle bacilli both in humans and cattle. The CD4 T-cell epitope repertoire was found to be more narrow in patients with active disease than in latently infected subjects. However, differential diagnosis of active TB could not be made reliably merely on the basis of epitope recognition. The mechanisms by which HLA polymorphism can influence the development of multibacillary tuberculosis (TB) need further analysis of epitopes, recognized by Th2 helper cells for B-cell responses. Future vaccine development would benefit from better definition of protective epitopes and from improved construction and formulation of subunits with enhanced immunogenicity. Epitope-defined serology, due to its operational advantages is suitable for active case finding in selected high disease incidence populations, aiming for an early detection of infectious cases and hence for reducing the transmission of infection. The existing knowledge of HLA class I binding epitopes could be the basis for the construction of T-cell receptor-like ligands for immunotherapeutic application. Continued analysis of the functions of mycobacterial epitopes, recognized by T cells and antibodies, remains a fertile avenue in TB research.

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“…Many immunogenetic factors are associated with host immune responses and susceptibility to M.tb in mice [3–7], including the major histocompatibility (MHC) haplotype (known as the H-2 haplotype in mice) [8–14]. A direct relationship between H-2 k and increased susceptibility to M.tb has been established, whereby the H-2 k alleles reduced survival of BALB/c H-2 k congenic mice following aerosol infection [9] and impaired the control of M.tb growth in the lungs following intraperitoneal infection [15].…”

Section: Introductionmentioning

confidence: 99%

H-2 alleles contribute to antigen 85-specific interferon-gamma responses during Mycobacterium tuberculosis infection

Beamer

Cyktor

Carruthers

et al. 2011

Cellular Immunology

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The in vitro immune responses to mycobacterial antigens have been linked to the H-2 loci in mice. We evaluated in vitro and in vivo immune responses during early Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2b), C57BL/6 (H-2k), CBA/J (H-2k), and C3H/HeJ (H-2k) mice to determine H-2k-dependent and -independent effects. H-2k-dependent effects included delayed and diminished Ag85-specific Th1 cell priming, a reduced frequency of Ag85-specific IFN-γ producing cells, reduced IFN-γ protein in vivo, and increased M.tb lung burden as demonstrated by C57BL/6 H-2k mice vs C57BL/6 mice. H-2k-independent factors controlled the amount of Ag85-specific IFN-γ produced by each cell, T cell numbers, granuloma size, and lymphocytic infiltrates in the lungs. Overall, these results suggest that an H-2k-dependent suboptimal generation of Ag85-specific cells impairs control of early M.tb growth in the lungs. H-2k-independent factors influence the potency of IFN-γ producing cells and on immune cell trafficking during pulmonary M.tb infection.

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Recessive expression of the H2A‐controlled immune response phenotype depends critically on antigen dose

Cited by 3 publications

References 32 publications

A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

Function and Potentials of M. tuberculosis Epitopes

H-2 alleles contribute to antigen 85-specific interferon-gamma responses during Mycobacterium tuberculosis infection

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