Tough antigens trigger immunity

The harder a protein is to chop up, say Delamarre and colleagues on page 2049, the more vigorous an immune response it will trigger. This suggests that the most durable antigens—or those attached to degradation-resistant carrier proteins—might make the best vaccines.

The correlation between stability and immunogenicity may seem counterintuitive, given that the very products of lysosomal degradation—antigenic peptides or epitopes—bind to class II MHC molecules for presentation to CD4⁺ T cells. And many (but not all) in vitro studies show that blocking lysosomal function in vitro inhibits antigen presentation.

To determine which kind of antigen elicits the strongest immune response, Delamarre et al. stuck identical T or B cell epitopes into lysosomal degradation-resistant and degradation-sensitive versions of the same protein. Mice immunized with the more durable versions of...