Are bacterial vaccine antigens T-cell epitope depleted?

For many infectious diseases, protective immunity can be elicited by vaccination with pathogen-derived proteins. Peptides derived from these proteins are bound to major histocompatibility complex (MHC) molecules and presented to T-cell receptors to stimulate an immune response. We show here that, paradoxically, bacterial proteins known experimentally to elicit a protective immune response are relatively depleted in peptides predicted to bind to human MHC alleles. We propose three nonconflicting reasons for this: the lack of precision of current predictive software, the low incidence of hydrophobic residues in vaccine antigens or evolutionary pressure exerted on bacteria by the immune system. We suggest that there is little value in predicting candidate vaccines based on high MHC-binding epitope density.