Delivery of Exogenous Antigens to Induce Cytotoxic CD8+ T Lymphocyte Responses

Abstract

Vaccines intended to induce a cytotoxic CD8+ T-cell response are highly sought after. However, some of these vaccines can be problematic if they replicate in the host. An alternative strategy is to exploit cross-presentation of exogenous antigens to express peptides on major histocompatibility complex (MHC) class I molecules. During cross-presentation, the delivered exogenous antigen can be taken up and processed through diverse mechanisms. Here, we will discuss the recent advances regarding the complex nature of the cross-priming process and the models that reflect its relevance in vivo. Moreover, we summarize current data that explore potential adjuvants and vaccine vectors that deliver antigens to activate CD8+ T cells relying on cross-presentation.

Figure 1

Antigen processing pathways. Direct presentation involves the processing of endogenously synthesized antigens (route A) by the proteasome (I) to break them down into smaller fragment (polypeptides) that are transported through the transporter associated with antigen processing (TAP) into the endoplasmic reticulum (II) for loading onto newly synthesized MHC class I molecules. These peptide-loaded MHC class I molecules are then transported through the Golgi (III) to the cell surface for presentation to CD8+ T cells. Considering the major route for antigen cross-presentation (route B), exogenous antigens are internalized in the endosome/phagosome before they are released into the cytosol and degraded by the proteasome to be presented on MHC class I molecules.