Identification of antigenic epitopes on human allergens: studies with HLA transgenic mice.

Abstract

Environmental factors play an important role in the rise and manifestation of allergic conditions in genetically predisposed subjects. Increased exposure to indoor/outdoor allergens is a significant factor in the development of allergic sensitization and asthma. Recently, strong relationships between the immune response to several highly purified allergens and specific human leukocyte antigen (HLA)-DQ and -DR haplotypes have been reported. The major antigens from clinically important allergens have been cloned and sequenced. However, whether innate structural features of major allergens or peculiar immune recognition of these molecules contribute to the overly robust immune responses is not known. We generated and used transgenic (tg) mice expressing single HLA class II transgene(s) to characterize the allergen epitopes presented by particular HLA class II molecules. Next, we generated in vivo models for asthma in the HLA tg mice by intranasal challenge with allergenic extracts. Furthermore, we used a single epitope to induce an allergic lung inflammation. Our system offers a sophisticated technique for systematically identifying the genetic (individual human class II) and antigenic (individual allergenic epitopes) basis of asthma sensitivity and has important implications for new treatment strategies.

Biology and function of neuroimmune semaphorins 4A and 4D

“…Mast cell activation, degranulation, and release of different inflammatory mediators are important pathophysiological events in allergy development [64]. Mastocytosis is a group of rare diseases characterized by mast cell proliferation and accumulation in different organs/tissues [65].…”

Novel foods and allergy: Regulations and risk-benefit assessment

“…Although currently no validated and widely accepted animal model is available, this is the most direct approach for determining the intrinsic sensitising potential of novel foods (Orruño & Morgan, 2006). A possible limitation for animal models is that certain allergies are associated with specific major histocompatibility complex (MHC) haplotypes, for which further refinement of animal models may be useful, such as the use of human-MHC-transgenic mice (Chapoval & David, 2003). Gubesch et al (2007) designed an approach to screen novel foods for the presence of pan-allergens, IgE binding of food allergens and clinical relevance of IgE binding.…”

Costimulation in Allergic Asthma: The Roles of B7 and Semaphorin Molecules

“…Allergic asthma is a Th2-driven, immunological chronic disease [1]. CD4+ T cells of Th2 phenotype secreting Th2 cytokines such as IL-4, IL-5, and IL-13 play a critical role in asthma initiation and propagation [2].…”

“…APC subdivide into "professional" such as dendritic cells (DC), B cells, and macrophages, and "unprofessional" such as epithelial cells, fibroblasts, basophils, eosinophils, ILC2 (type 2 innate lymphoid cells), which normally have other functions in tissues and do not act as APC [3][4][5]. Antigenic epitopes derived from a captured allergen are presented to T cells in the context of specific MHC (human leukocyte antigen, HLA, for human cells) molecules [1]. This is the first signal for T cell activation, whereas a second signal is derived from costimulation where specific costimulatory molecules on APC interact with their receptors on T cells (Figure 1) [6].…”