Mechanisms of immunotherapy: IgG revisited

Wachholz, Petra A.; Durham, Stephen R.

doi:10.1097/01.all.0000136753.35948.c0

Cited by 175 publications

(150 citation statements)

References 51 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Secondly, induction of PUTGAspecific Tregs or Th1 cells may help in the regulation, through bystander mechanisms (26), of Th2 responses directed against known TG allergens present in the same pollen particle. Thirdly, the regulation of PUTGA-specific Th2 responses may also result in downstream regulation of IgE and induction of blocking IgG antibody responses to known TG allergens, a hallmark of specific immunotherapy (SIT) treatment (27,28). Finally, induction of PUTGA-specific Th1 or Treg cells may lead to PUTGA-specific IgG production, which may interfere with IgE-induced mediator release and other immediate-type reactions by mechanisms such as steric hindrance, competition for antigen binding, and inhibitory signaling through FcγRIIB (29,30).…”

Section: Discussionmentioning

confidence: 99%

Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals

Schulten

Greenbaum

Hauser

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

T cells play an important role in the pathogenesis of allergic diseases. However, the proteins considered as potential immunogens of allergenic T-cell responses have traditionally been limited to those that induce IgE responses. Timothy grass (TG) pollen is a well-studied inhaled allergen for which major IgE-reactive allergens have also been shown to trigger T helper 2 (Th2) responses. Here we examined whether other TG pollen proteins are recognized by Th2 responses independently of IgE reactivity. A TG pollen extract was analyzed by 2D gel electrophoresis and IgE/IgG immunoblots using pooled sera from allergic donors. Mass spectrometry of selected protein spots in combination with de novo sequencing of the whole TG pollen transcriptome identified 93 previously undescribed proteins for further study, 64 of which were not targeted by IgE. Predicted MHC binding peptides from the previoulsy undescribed TG proteins were screened for T-cell reactivity in peripheral blood mononuclear cells from allergic donors. Strong IL-5 production was detected in response to peptides from several of the previously undescribed proteins, most of which were not targeted by IgE. Responses against the dominant undescribed epitopes were associated with the memory T-cell subset and could even be detected directly ex vivo after Th2 cell enrichment. These findings demonstrate that a combined unbiased transcriptomic, proteomic, and immunomic approach identifies a greatly broadened repertoire of protein antigens targeted by T cells involved in allergy pathogenesis. The discovery of proteins that induce Th2 cells but are not IgE reactive may allow the development of safer immunotherapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals

Schulten

Greenbaum

Hauser

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…41 Moreover, it might be more important to measure the blocking activity via in vitro assays at an allergen-specific level. 65,68 Shift of the Th1 / Th2 Cytokine Ratio…”

Section: Discussionmentioning

confidence: 99%

“…67 In addition to the increase of specific IgG4 levels, SIT increases the blocking activity of IgG on the allergen capture and cross-linking of mast cell and basophil Fcε-receptor bound IgE. 68 Moreover, IgG4 does not activate the complement system, has a lower affinity for Fcγ receptors, interferes with basophil histamine release and reduces antigen-specific T cell proliferation by prevention of IgE-facilitated allergen binding to B cells and subsequent antigen-presentation. 65,68 Formation of multivalent IgE-IgG-allergen complexes has been suggested to result in mast cell FcεRI autoinhibition.…”

Section: Allergen-specific Regulatory Cellsmentioning

confidence: 99%

“…68 Moreover, IgG4 does not activate the complement system, has a lower affinity for Fcγ receptors, interferes with basophil histamine release and reduces antigen-specific T cell proliferation by prevention of IgE-facilitated allergen binding to B cells and subsequent antigen-presentation. 65,68 Formation of multivalent IgE-IgG-allergen complexes has been suggested to result in mast cell FcεRI autoinhibition. After binding of the allergen-IgG4 complex to the inhibitory FcγRIIb, this is phosphorylated by FcεRI-associated kinases.…”

Section: Allergen-specific Regulatory Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Novel developments in the mechanisms of immune tolerance to allergens

Eiwegger

Gruber

Szépfalusi

et al. 2012

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…The production of specific IgG antibodies to allergens, especially IgG4 subclass, is the most important immunological change induced by AIT [59][60][61][62]. However, in some studies there is a lack of correlation between increased IgG4 titres and clinical improvement [55], since the induction of IgG4 blocking antibodies may not be reflected in serum or other biological fluid samples, requiring bioassays as the inhibition of IgE-facilitated allergen presentation for its possible detection [63].…”

Section: Immunotherapy Follow-upmentioning

confidence: 99%

Allergen-Specific Immunotherapy Follow-Up by Measuring Allergen-Specific IgG as an Objective Parameter

Taketomi¹,

Miranda²,

Júnior³

et al. 2017

Immunotherapy - Myths, Reality, Ideas, Future

View full text Add to dashboard Cite

The clinical efficacy of the allergen-specific immunotherapy (AIT) has been well-documented using inhalant or hymenoptera-derived allergens in atopic patients with corresponding specific IgE antibodies. AIT is considered as the unique treatment that is capable of modifying the natural course of the allergic disease because it induces a variety of immunological mechanisms, with emphasis in the production of blocking IgG antibodies by IL-10-stimulated B cells due to the generation of Treg, Breg, or even Th2 cells. Thus, the measurement of specific IgG subclasses, particularly IgG4, to the crude extract or more importantly to allergen components, might be a useful and potential tool to follow-up objectively the patients undergoing AIT in addition to clinical parameters. In this chapter, the authors have emphasized a very sensitive and highly specific reverse ELISA, developed by them, to measure IgG subclasses directed to clinically relevant natural allergens that are undoubtedly better when compared to those obtained with recombinant counterparts. Such a technique may produce more authentic results taking into account the IgG subclass binding capacity to a particular allergen and might be a valuable and alternative method for monitoring activation of tolerance-inducing mechanisms in patients under AIT.

show abstract

Mechanisms of immunotherapy: IgG revisited

Cited by 175 publications

References 51 publications

Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals

Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals

Novel developments in the mechanisms of immune tolerance to allergens

Allergen-Specific Immunotherapy Follow-Up by Measuring Allergen-Specific IgG as an Objective Parameter

Contact Info

Product

Resources

About