Major histocompatibility complex class I (MHC-I) (MHC-I)

Major histocompatibility complex class I (MHC-I) molecules are cell surface glycoproteins that play a fundamental role in the adaptive immune system by presenting peptide antigens to CD8+ cytotoxic T cells (StatPearls, 2023). While expressed on all nucleated cells, their presence on dendritic cells (DCs) is unique due to the process of cross-presentation, where DCs internalize extracellular antigens and present them on MHC-I to prime naive T cells (Nature Reviews Immunology, 2018). This mechanism is vital for generating an effective immune response against viruses and tumors that do not directly infect DCs. In therapeutic contexts, MHC-I on DCs is the focal point for cancer vaccines and dendritic cell-based therapies, such as Sipuleucel-T, which aim to load these molecules with tumor-specific antigens to stimulate a robust anti-tumor response (FDA, 2010). However, many tumors evade the immune system by downregulating MHC-I expression or through mutations in the antigen-presentation machinery, presenting a significant challenge for these therapies (PubMed, 2021). Understanding the dynamics of MHC-I on DCs is therefore crucial for developing next-generation immunotherapies and overcoming resistance mechanisms in oncology.

Other names

HLA class IHuman leukocyte antigen class IMHC-IClass I MHCAntigen-presenting molecule MHC-I

Facilitates the presentation of endogenous and cross-presented exogenous peptide antigens to the T-cell receptor (TCR) of CD8+ T cells, leading to T-cell activation, proliferation, and the generation of cytotoxic effector functions.