Human leukocyte antigen class I and class II molecules presenting tumor neoantigens (HLA-neoantigen complex)

Human leukocyte antigen (HLA) class I and class II molecules are cell surface proteins responsible for presenting peptide fragments to the immune system (Janeway et al., Immunobiology, 2001). In the context of personalized cancer immunotherapy, these molecules present vaccine-encoded tumor neoantigens—mutated proteins unique to a patient's cancer cells—to T-cell receptors (TCRs) (Sahin & Türeci, Science, 2018). HLA class I molecules typically present these peptides to CD8+ cytotoxic T cells, while HLA class II molecules present them to CD4+ helper T cells (Nature Reviews Cancer, 2021). This presentation is a critical step in the cancer-immunity cycle, as it allows the immune system to recognize and selectively destroy malignant cells while sparing healthy tissue (Chen & Mellman, Immunity, 2013). Therapeutic strategies targeting this complex include personalized mRNA or peptide vaccines, such as mRNA-4157/V940, designed to expand the population of neoantigen-specific T cells (Moderna/Merck, 2023). The efficacy of these treatments depends heavily on the patient's specific HLA alleles and the successful processing and loading of the neoantigenic peptides onto the HLA molecules (PubMed, 2022).

Other names

MHC-peptide complexNeoantigen-HLA complexTumor-specific antigen-HLA complexpMHC complexMajor histocompatibility complex-peptide complex

Presentation of vaccine-derived tumor-specific neoantigen peptides to T-cell receptors (TCRs) to induce a targeted cytotoxic (CD8+) and helper (CD4+) T-cell immune response against tumor cells.