Dendritic cell cross-presentation

Dendritic cell cross-presentation is a specialized biological process through which professional antigen-presenting cells, primarily conventional type 1 dendritic cells (cDC1), capture extracellular antigens and present them on MHC class I molecules to activate CD8+ T cells [1, 2, 6]. Unlike the classical antigen presentation pathway that displays endogenous proteins, cross-presentation allows the immune system to recognize and mount a cytotoxic response against tumors and viruses that do not directly infect the dendritic cells [2, 6]. This process is vital for anti-tumor immunity and is a primary focus for the development of cancer vaccines and immunotherapeutic adjuvants [8, 10, 12]. Drugs targeting this pathway typically function by enhancing antigen delivery to cDC1 via specific receptors like CLEC9A or by using Toll-like receptor (TLR) agonists to trigger dendritic cell maturation and efficient peptide loading [8, 10]. Dysfunction in cross-presentation can lead to immune evasion by pathogens and malignancies, whereas its over-activation may result in autoimmune pathology [4].

Other names

Antigen cross-presentationCross-primingVacuolar pathwayEndosome-to-cytosol pathwayExogenous MHC class I presentation

Enhancement of exogenous antigen uptake, stabilization of endosomal pH, recruitment of TAP and Sec61 to endosomes, and licensing of dendritic cells to promote MHC class I peptide loading and subsequent CD8+ T cell priming.