Autologous tumor antigen-derived peptide-HLA complex (pHLA) (pHLA complex)

Autologous tumor antigen-derived peptide-HLA complexes are the molecular targets recognized by the cellular arm of the adaptive immune system on the surface of malignant cells. These complexes consist of a short peptide fragment, derived from the degradation of intracellular tumor-specific or tumor-associated proteins, bound within the groove of a Human Leukocyte Antigen (HLA) molecule [PMID: 30103341]. This presentation allows T-cells to monitor the internal protein composition of a cell, identifying mutations (neoantigens) or abnormally expressed proteins (shared antigens) that signal oncogenic transformation [PMID: 26642438]. Therapeutic interventions such as T-cell receptor (TCR) engineered T-cells, tumor-infiltrating lymphocytes (TILs), and cancer vaccines specifically target these complexes to induce a potent cytotoxic response against tumor cells [PMID: 33571153]. Because these targets encompass the entire intracellular proteome, they offer a significantly larger target space than traditional cell-surface proteins [PMID: 29735921]. However, the effectiveness of these therapies is often limited by the high polymorphism of HLA alleles across the human population and the ability of tumors to evade immune detection by downregulating HLA expression or components of the antigen-processing machinery [PMID: 30718319].

Other names

pMHCPeptide-MHC complexTumor-specific peptide-HLA complexNeoantigen-HLA complexAntigen-presenting complexTumor antigen-derived peptide-MHC complex

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) or TCR-mimetic molecules, leading to the formation of an immunological synapse and subsequent cytotoxic T-lymphocyte (CTL) mediated lysis of the tumor cell.