Peptide Immunotherapy
Section snippets
In vitro and in vivo experimental models
The concept of therapeutic, antigen-specific targeting of T cells for the prevention and treatment of immunologic diseases developed from in vitro studies documenting the effects of high-dose peptide presentation between T cells. CD4+ helper T-cell clones were rendered refractory to antigen stimulation following pretreatment with supraoptimal concentrations of specific peptide [2]. Because antigen-presenting cells were absent, presentation of peptide to T-cell receptors most likely occurred
Autoimmunity
Peptide immunotherapy has been evaluated in small clinical studies with varying degrees of success. Most studies have focused on individuals with allergic disease, but some have also been performed in autoimmune disease including type I diabetes, rheumatoid arthritis, and multiple sclerosis. In many autoimmune diseases, it remains unclear which antigens should be selected as targets for intervention. Multiple sclerosis studies have focused on peptides from MBP, whereas two recent studies have
Mechanisms of peptide-induced tolerance
Immunologic tolerance in the T-cell compartment is likely to arise through systemic presentation of peptides (which are delivered to the immune system in saline without adjuvant and at very low doses) to naïve T cells by nonprofessional antigen-presenting cells and steady state (quiescent) dendritic cells, both of which are known to induce tolerogenic T-cell responses [41]. Because the peptides are encountered in a noninflammatory environment, the T-cell response will be one of tolerance
The role of peptide dose in therapy
Little is known about the most effective dose for induction of tolerance through peptide therapy. In mice, tolerogenic peptide doses range from a few micrograms [45] to milligrams [46]. By delivering T-cell epitopes directly to dendritic cells in vivo, it has recently been shown that doses as small as 500 pg can induce tolerance in a murine model [47]. Fundamental differences may exist in the mechanisms of low- and high-dose tolerance. High-dose protocols have been associated with clonal
Summary
Synthetic peptides representing T-cell epitopes of allergens and autoantigens have been employed to induce antigen-specific tolerance in vivo in experimental models and the clinical setting. Delivery of peptides orally or by injection leads to reduced reactivity to antigen accompanied by the induction of T cells with a regulatory phenotype. In most models, production of IL-10 (and occasionally TGF-β) has been increased, whereas PBMC secretion of Th1 and Th2 cytokines is reduced. Peptide therapy
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Cited by (16)
Antigenic cross-reactivity between Schistosoma mansoni and pollen allergens from the birch tree (Betula verrucosa) and Timothy grass (Phleum pratense): involvement of shared glycan epitopes and implications for the hygiene hypothesis
2018, International Journal for ParasitologyCitation Excerpt :If true, the idea could be relevant for specific immunotherapy (SIT) of allergic disorders. Currently allergic desensitisation often involves vaccine-type administration of increasing doses of extracts of individual or several allergens (Larche, 2006; Larche et al., 2006; Fujita et al., 2012). SIT is the only treatment approved by the World Health Organization (WHO) for the treatment of allergic diseases apart from allergen avoidance (Bullimore et al., 2012).
A novel IgE-binding epitope of cat major allergen, Fel d 1
2016, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The overall results indicated that the epitope of the MAbC48 is allergenic (induced specific IgE generation) in humans. Information on repertoire of antigenic sites, especially the IgE binding epitopes of a particular allergen is necessary not only for understanding the immune responses to the allergen and the allergen cross-reactivity, but also for generating engineered hypoallergenic variants of the protein or a defined allergen molecule for a more efficacious specific component resolved immunotherapy or personalized allergen vaccine design [22–28]. Several strategies have been applied to identify the B cell epitopes of allergens including: use of overlapping synthetic peptides [12]; mimotope mapping using phage display peptide library [27], peptide microarray immunoassay [29], X-ray crystallographic and NMR-based techniques [27,30–33], computational (in silico) methods [34,35], and specific monoclonal antibody binding and IgE inhibition assay [36,37].
Immunotherapy of allergic disease
2013, Clinical Immunology: Principles and Practice: Fourth EditionDifferences in venom and cuticular peptides in individuals of Apis mellifera (Hymenoptera: Apidae) determined by MALDI-TOF MS
2010, Journal of Insect PhysiologyDetection of Honeybee Venom in Envenomed Tissues by Direct MALDI MSI
2009, Journal of the American Society for Mass SpectrometryCitation Excerpt :Honeybee venom (HBV) is one of the best characterized venoms amongst hymenoptera. Its composition, isolation, characterization, and the cloning of its bioactive species induced physiological damages and use in therapeutic treatments, are some of the aspects so far investigated [9, 22, 38, 39]. Here, the use of a novel technology named MALDI MSI is applied to the detection of HBV in envenomed tissues.
Immunotherapy of allergic disease: Factors Associated with Adverse Reactions to Specific Allergen Immunotherapy
2008, Clinical Immunology: Principles and Practice Expert Consult: Online and Print
The author is an Asthma UK Senior Research Fellow.