Mutant Kirsten rat sarcoma virus oncogene homolog-derived peptide epitopes presented on Major Histocompatibility Complex class II (Mutant KRAS-MHC II complex)

Mutant KRAS-derived peptide epitopes presented on MHC class II are neoantigens that play a pivotal role in the immune system's ability to recognize and eliminate cancer cells. KRAS is a GTPase involved in signal transduction, and mutations at codons 12, 13, or 61 are among the most common drivers in human malignancies, including pancreatic, colorectal, and lung cancers (PubMed: 33009416). While MHC class I molecules present antigens to CD8+ cytotoxic T cells, MHC class II molecules (such as HLA-DR, DQ, and DP) present processed mutant KRAS peptides to CD4+ helper T cells. This interaction is crucial for a comprehensive anti-tumor response, as CD4+ T cells provide essential help for the recruitment and maintenance of CD8+ T cells and can also exert direct effector functions (NEJM: 10.1056/NEJMoa1609279). Therapeutic interventions targeting these complexes include neoantigen vaccines and T-cell receptor (TCR) engineered T-cell therapies, which aim to exploit the high specificity of these mutant sequences. Because these epitopes arise from somatic mutations found only in tumor cells, they represent highly attractive targets for precision immunotherapy with a low risk of systemic autoimmunity (Nature: 10.1038/s41586-022-04485-w).

Other names

KRAS neoantigensMutant KRAS HLA-II complexesKRAS-derived neoepitopesMutant KRAS-HLA-DR/DQ/DP complexes

Recognition of the mutant peptide-MHC II complex by the T-cell receptor (TCR) on CD4+ T cells, leading to T-cell activation, cytokine production, and orchestration of an anti-tumor immune response.