Mutant KRAS-derived peptide-MHC class II complex (Mutant KRAS-pMHCII)

The Mutant KRAS-derived peptide-MHC class II complex is a highly specific neoantigen target formed when mutated KRAS proteins (such as G12D, G12V, or G12C) are processed and presented on Major Histocompatibility Complex (MHC) class II molecules. While KRAS is a well-known membrane-bound GTPase that drives oncogenesis in pancreatic, colorectal, and lung cancers, its mutant fragments serve as intracellular antigens that can be displayed on the cell surface for immune surveillance (Simanshu et al., 2017, Cell). Presentation on MHC class II is particularly significant as it allows for the activation of CD4+ helper T cells, which are essential for orchestrating durable anti-tumor immunity and can sometimes exert direct cytotoxic effects (Bear et al., 2020, Nature Reviews Cancer). Therapeutic interventions targeting these complexes include adoptive cell transfer using T-cell receptors (TCRs) engineered to recognize specific mutation-HLA combinations, as well as therapeutic vaccines designed to expand endogenous T-cell populations (Leidner et al., 2022, NEJM). Because these epitopes are derived from somatic mutations absent in healthy tissue, they offer a narrow therapeutic window with the potential for high tumor specificity, though efficacy is often limited by the high polymorphism of HLA alleles and the immunosuppressive tumor microenvironment (Tran et al., 2016, NEJM).

Other names

KRAS neoantigen-MHC II complexMutant KRAS peptide-HLA class II complexKRAS G12D peptide-HLA-DRB1*08:01 complexKRAS G12V peptide-MHC II complexMutant KRAS-presented CD4+ T cell epitope

Recognition of the specific mutant KRAS peptide fragment bound within the MHC class II groove by the T-cell receptor (TCR) of CD4+ T cells, leading to T-cell activation, cytokine production (e.g., IFN-gamma), and coordination of an anti-tumor immune response (Leidner et al., 2022, NEJM).