Mesothelin-derived peptide–major histocompatibility complex class I complex

The term **“Mesothelin peptide:MHC complex”** refers not to a single protein receptor but to the **complex formed when short peptides derived from the tumor-associated antigen mesothelin (MSLN) are bound in the peptide-binding groove of a major histocompatibility complex (MHC) molecule, typically MHC class I, and displayed on the cell surface for recognition by T cells**. MHC class I molecules bind intracellularly generated peptides of around 8–10 amino acids in a groove formed by an α‑helical “roof” over a β‑sheet “floor”; the peptide’s side chains occupy defined binding pockets, and the resulting peptide–MHC (pMHC) complex is the ligand recognized by the T‑cell receptor. Mesothelin itself is a GPI‑anchored surface glycoprotein highly overexpressed on many solid tumors, including ovarian, pancreatic, and lung cancers, and is being extensively explored as a therapeutic target. Proteasomal processing of mesothelin and subsequent transport of mesothelin-derived peptides into the endoplasmic reticulum allow loading onto MHC class I within the peptide-loading complex, after which stable mesothelin peptide–MHC complexes traffic to the cell surface. These complexes are central to **CD8⁺ T‑cell recognition of mesothelin-expressing tumor cells**, and they constitute the **true molecular target** for natural and engineered T‑cell responses; however, “mesothelin peptide:MHC complex” is not a standardized, single canonical target name but a functional description spanning many possible mesothelin epitopes and MHC alleles, which is why the designation is considered **non‑standard/overly generic (is_incorrect: true)** for a unique molecular target.

Other names

Mesothelin peptide–MHC complexMesothelin peptide–MHC class I complexMesothelin peptide–HLA class I complexMesothelin-derived epitope–MHC complexMesothelin peptide–MHC antigenic complex

T‑cell engagement and cytotoxicity driven by T‑cell receptor recognition of tumor-associated mesothelin-derived peptides presented on MHC class I molecules (peptide–MHC as the physiological ligand for TCRs)