Peptide–MHC complexes: dressing up to manipulate T cells against autoimmunity and cancer

Antigen-specificity of T cells provides important clues to the pathogenesis of T cell-mediated autoimmune diseases and immune-evasion strategies of tumors. Identification of T cell clones involved in autoimmunity or cancer is achieved with soluble peptide–MHC (pMHC) complex multimers. Importantly, these complexes can also be used to manipulate disease-relevant T cells to restore homeostasis of T cell-mediated immune response. While auto-antigen-specific T cells can be deleted or anergized by T cell receptor engagement with cognate pMHC complexes in the absence of costimulation, integration of these complexes in artificial antigen-presenting systems can activate tumor antigen-specific T cells. Here the authors discuss the advancements in pMHC-complex-mediated immunotherapeutic strategies in autoimmunity and cancer and identify the lacunae in these strategies that need to be addressed to facilitate clinical implementation.