What makes a protein immunogenic, particularly for strong T cell–mediated immunity? To a first approximation, this determination seems to be made by dendritic cells (DCs). Immature DCs, as in skin 1,2,3,4, lung 5, blood 6,7, and spleen 7,8, take up proteins, immune complexes, microbes, and dying cells. However, in order to use these antigens to stimulate a T cell response, the DCs must undergo a characteristic process of terminal differentiation called “maturation.” The known stimuli for DC maturation are numerous and include inflammatory cytokines, CD40 ligand (CD40L), viral and microbial constituents such as double-stranded RNA and LPS, and certain CpG oligonucleotides.
Maturation changes DCs in many ways that help explain their potent immunogenicity. Examples include de novo expression of T cell costimulatory molecules like CD86...
