T-cell receptor recognizing Amb a 1-derived peptides presented by MHC II (TCR-Amb a 1-MHC II)

The T-cell receptor (TCR) recognizing Amb a 1-derived peptides presented by MHC II is a pivotal molecular complex in the development of seasonal allergic rhinitis caused by short ragweed (Ambrosia artemisiifolia) [1]. Amb a 1 is a 38-kDa pectate lyase and the major allergen of ragweed pollen, recognized by over 90% of ragweed-allergic individuals [2]. The interaction occurs when Amb a 1 is processed by antigen-presenting cells and its peptides are displayed on Major Histocompatibility Complex class II (MHC II) molecules, such as HLA-DRB1*01:01, to be recognized by specific CD4+ T cells [3]. This recognition triggers a Th2-biased immune response, leading to the secretion of pro-inflammatory cytokines like IL-4, IL-5, and IL-13, which facilitate IgE class switching and eosinophil recruitment [4]. Therapeutic targeting of this TCR-peptide-MHC complex is the basis for allergen-specific immunotherapy (ASIT), including sublingual products like Ragwitek [5]. These treatments aim to induce immune tolerance by promoting the expansion of regulatory T cells (Tregs) and the production of blocking IgG4 antibodies, thereby neutralizing the allergic cascade upon subsequent environmental exposure [6]. Modulating this specific TCR interaction is essential for long-term disease modification rather than just symptomatic relief. Challenges in targeting this receptor include the high diversity of TCR repertoires among different patients and the risk of triggering systemic allergic reactions during treatment.

Other names

Amb a 1-specific T-cell receptorRagweed allergen-specific TCRAmb a 1-reactive TCRTCR-Amb a 1-HLA-DR complex

Induction of peripheral T-cell tolerance and regulatory T-cell expansion through controlled allergen exposure.