Table of Contents

Component

g205 Phl p 1

g205 Phl p 1 Scientific Information

Type:

Component

Name; WHO/IUIS:

Phl p 1

Biological function:

b-Expansin

Allergen code:

g205

Route of Exposure:

Airway

Source Material:

Grass pollens Timothy grass allergen components

Summary

Phl p 1 allergen derived from timothy grass (Phelum pratanse) pollen is one of the distinguished group 1 grass pollen allergens (1, 2). Group 1-grass pollen allergens are glycosylated proteins with a molecular weight of ~30 kDa that appear as cross-reactive antigens in majority of the grasses and corn species (3). Group 1 grass pollen allergen belongs to the subclass beta-expansin (EXP-B) of the expansin protein superfamily, which is involved in cell wall loosening and extension in the plants (4).

Phl p 1, the major allergen of timothy grass is identified by more than 90% of grass pollen-allergic patients. This allergen is highly cross-reactive among all the grass species of temperate and tropical regions (1, 5) and shows 90% sequence identity with allergens of other members of the Pooideae subfamily (5). A major IgE-reactive segment of Phl p 1 allergen reveals a substantial sequence identity of about 40% with the family of immunoglobulin domain-like group 2/3 grass pollen allergens (3).

Phl p 1 initiates sensitization in majority of the pediatric allergic rhinitis (AR) patients, followed by sensitization of these patients to other timothy grass pollen allergens (such as Phl p 5, Phl p 4, Phl p 2, and Phl p 6, and Phl p12) (6).

Recombinant pollen allergens aid in lowering the number of allergens required for appropriate diagnosis of grass pollen allergy. Only a limited number of recombinant timothy grass pollen allergens results in the determination of a high percentage of patients with grass pollen-specific IgE. This indicates the benefits of recombinant allergens not only for in vitro diagnosis but also to evaluate the specific percentage of IgE produced by individuals against some allergens (7).

Epidemiology

Worldwide distribution

Phl p 1 allergen is found in grass species of both temperate and tropical regions of the world (2). A study using sera from European, Asian, and American subjects assessed the percentage of IgE directed to pollen extracts from nine different monocot species including rPhl p 1, rPhl p 2, rPhlp 5 of timothy grass and rBet v 2 of birch pollen. The study results showed that IgE antibodies to these four recombinant pollen allergens accounted for a mean of 59% (8). A study from China detected that out of all timothy grass serum(s) IgE positive patients only 17.1% were positive to the antigen Phl p 1 and 100% were positive to Phl p 4 (9). A longitudinal birth cohort study in Germany investigated the evolution of IgE sensitization to P. pratense allergenic molecules in children suffering from seasonal AR due to grass pollens. The study detected Phl p1 initiated sensitization in more than 75% of these patients followed by sensitization to other allergens. Moreover, Phl p 1, Phl p 5, and Phl p 4 were the most frequently identified molecules in the preclinical sensitization phase (6).

Environmental Characteristics

Source and tissue

All grass species are pollinated by wind and during the peak flowering season they release allergenic pollen grains (5). The allergenic glycoprotein Phl p 1 has been found to be localized in the cytoplasm and the outer layer (exine) of mature pollen grains of grasses (10, 11) and these allergens are released from the pollen grain on hydration (5).

Figure 1: Timothy grass (P. pratense) major pollen allergen Phl p 1 (12)

Figure 2: Timothy grass (P. pratense) within pollen grains by fluorescence microscopy and after immunogold silver staining at the light microscopic. (12)

Risk factors

Röschmann et al. (2011) studied the response of airway epithelium to Phl p 1, with an aim to obtain an insight into the immunostimulatory capacity of Phl p 1. They observed that Phl p 1 triggers the release of a wide range of mediators (IL-6, IL-8, TGF-β), which in turn attract and influence the immunocompetent cells’ activities. Hence, Phl p 1 is a powerful inducer of the immune system and linked with allergic respiratory diseases, especially AR (13) .

Clinical Relevance

Specific molecules

Recombinant Phl p 1 (rPhl p 1) is a non-glycosylated protein produced in an Escherichia coli (E. coli) strain that carry a cloned cDNA encoding P. pratense allergen Phl p 1. rPhl p 1 closely resembles the natural Phl p 1 and binds to IgE in majority of the patients with grass pollen allergy, indicating that rPhl p 1 shares many of the IgE epitopes with natural group 1 grass pollen allergens (10). rPhl p 1 is considered to be one of the most important “species specific allergens” of timothy grass followed by rPhl p 5 (14). Scaparrotta and colleagues (2013) detected rPhl p1 to be the predominant sensitizing allergen at all ages of pediatric population and at all levels of timothy grass pollen specific IgE molecules (14). Another study assessing specific IgE levels to the clinically relevant timothy grass pollen allergens found the level of Phl p 1 to be significantly higher (p=0.02) in children with moderate AR than in children with mild AR indicating the ability of Phl p 1 to induce allergic symptoms in AR patients (15).

Douladaris et al. (2019) constructed a recombinant hybrid molecule with four major timothy grass pollen allergens, Phl p 1, Phl p 2, Phl p 3, and Phl p 6 for in vitro serological testing and in vivo diagnosis of grass pollen allergy in adult patients. The success of this hybrid molecule suggested that all grass pollen allergen patients showed IgE reactivity and also positive skin reaction to this molecule (16).

Cross-reactive molecules

IgE antibodies from grass pollen allergic patients and also group 1 specific antibodies are found to cross-react with natural group 1 grass pollen allergens of different grass species (10). rPhl p 1 has been shown to inhibit IgE antibody binding to most of the group 1 isoallergens from 7 to 8 grass species indicating wide-spread cross reactivity between different grass species (7, 10). Hence, a single recombinant group 1 allergen contains many of the IgE epitopes of group 1 isoallergenic variants from several different grass species (10). The major timothy grass pollen allergen Phl p 1 shows cross-reactivity with most grass, corn, and monocot-derived group 1 allergens (17).

Molecular Aspects

Biochemistry

Recombinant Phl p1 protein of timothy grass has a molecular weight of 27 kDa (18). Unlike the native Phl p 1, which has N-glycosylation and contains glycans (11), the recombinant allergen is unglycosylated. Phl p 1 contains 7 cysteine residues (3). Phl p 1 are 31-35 kDa glycoproteins, belongs to EXPB protein family, and help in pollen tube growth (4).

Isoforms, epitopes, and antibodies

Phl p1 allergen has two isoforms of molecular weights of 37 kDa and 38 kDa (19). Each isoform of Phl p 1 has two isoallergens (Phl p 1.0101 and Phl p 1.0102) (14).

Phl p 1 consists of the majority of group 1-specific T- cell epitopes (1). The analysis of Phl p 1 IgE epitopes using rPhl p1 fragments revealed the presence of multiple continuous IgE epitopes. The prominent one being present in the C-terminal end of Phl p 1 and this intact folded Phl p1 domain indicates the primary targets of patients’ IgE antibodies (3). A study by Madritsch et al. (2015) determined three independently accessible IgE epitopes available on the surface of Phl p 1 (1).

Phl p 1 contains most of the group 1-specific IgE. More than 90% of the grass pollen allergic patients show IgE reactivity to group 1 allergen and elicit most of the allergic symptoms (1, 16).

Cross reactivity

Phl p 1 allergens are extremely cross-reactive allergens in majority of the grass species of temperate and tropical regions (1).

Diagnostic Relevance

AIT Prescription

Allergic Immunotherapy (AIT)

The use of allergen immunotherapy (AIT) have increased owing to rise in the number of patients with respiratory allergic disease and have shown long-term benefits (20). The development of recombinant allergens (such as rPhl p1) helps to develop patient-tailored immunotherapy (7).

Exposure

The major grass pollen allergens, such as Phl p 1 are usually present within the pollen grain in a typical pattern and at the time of activation, allergen moves from the exine of the pollen grain to the surface in order to be released (5, 11, 12). Activation of the pollen grain leads to allergen release (normally under humid condition) at the mucosal surface of the nose and triggers allergic reactions (12).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: October 2020

References

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