Aspergillus fumigatus peptide–Major Histocompatibility Complex (Af-pMHC)

Aspergillus fumigatus peptide–Major Histocompatibility Complex (MHC) complexes are molecular structures formed when host antigen-presenting cells (APCs) process fungal proteins and display the resulting peptides on their surface (Kumaresan et al., 2014, JCI). These complexes are essential for the adaptive immune system to recognize and respond to invasive aspergillosis, a life-threatening fungal infection primarily affecting immunocompromised patients (Bacher et al., 2014, Mucosal Immunol). The peptides are typically derived from highly expressed fungal cell wall proteins, such as Crf1 or Gel1, and are presented by either MHC Class I or Class II molecules to activate CD8+ or CD4+ T cells, respectively (Stuehler et al., 2011, Blood). In a therapeutic context, these pMHC complexes serve as highly specific targets for novel immunotherapies, including T-cell receptor (TCR)-like antibodies and chimeric antigen receptor (CAR) T cells (Kumaresan et al., 2014, JCI). By targeting these complexes, therapies can bypass the need for traditional antifungal drugs and directly leverage the host's immune machinery to eliminate the pathogen or infected cells. However, the diversity of human HLA alleles and the potential for cross-reactivity with self-peptides present significant challenges in the development of universal pMHC-targeted treatments (Schubert et al., 2010, J. Immunol). Research into these complexes aims to provide a more precise alternative to broad-spectrum antifungals, which often suffer from toxicity and rising resistance.

Other names

Aspergillus fumigatus pMHCFungal peptide-MHC complexAspergillus-specific pMHCAf-pMHC complex

Binding of therapeutic agents (TCRs or TCR-like antibodies) to the specific fungal peptide presented within the MHC groove, triggering an immune-mediated cytotoxic response against the fungal pathogen or infected host cells.