Major allergen I (Fel d 1) (Fel d 1)

Major allergen I (Fel d 1) is the primary protein responsible for cat-induced allergic reactions, affecting up to 95% of cat-allergic individuals [1.3.1, 1.4.2]. It is a secretoglobin protein complex, structurally characterized as a tetrameric glycoprotein composed of two non-covalently linked heterodimers, each consisting of two disulfide-linked polypeptide chains [1.3.3, 1.4.1]. While its endogenous function in cats is not fully elucidated, it is hypothesized to be involved in pheromone transport, lipid binding, or skin protection [1.3.1, 1.4.4]. In humans, Fel d 1 acts as a potent allergen that triggers IgE-mediated hypersensitivity, leading to conditions such as allergic rhinitis, conjunctivitis, and asthma [1.1.1, 1.4.2]. Therapeutic interventions targeting Fel d 1 include allergen-specific immunotherapy (AIT) to induce immune tolerance, monoclonal antibodies (e.g., REGN1908/REGN1909) to neutralize the allergen, and innovative approaches like anti-Fel d 1 IgY-enriched diets or vaccines for cats to reduce allergen shedding [1.1.2, 1.3.2, 1.5.3]. The protein's stability and small particle size allow it to remain airborne for long periods and persist in environments even where cats are not present, making it a challenging target for environmental control [1.3.2, 1.4.2]. Recent research also suggests that Fel d 1 may enhance innate immune signaling through TLR4 and TLR2, potentially explaining its high allergenicity [1.2.2].

Other names

Felis domesticus allergen 1Major allergen I polypeptide chain 1Major allergen I polypeptide chain 2AG4Allergen Cat-1

The primary mechanisms of action for drugs targeting Fel d 1 include: (1) passive immunization via monoclonal antibodies (e.g., REGN1908/REGN1909) or IgY to neutralize the allergen's IgE-binding epitopes; (2) allergen-specific immunotherapy (AIT) using recombinant proteins or peptides (e.g., Cat-PAD) to induce T-cell tolerance and shift the immune response from Th2 to Th1/Treg; and (3) active immunization of the source (cats) to reduce the secretion of active Fel d 1.