Targeting of exogenous protein antigens to a novel endosomal processing pathway for class I-restricted presentation

CD8+ cytotoxic T lymphocytes (CTL) mediate protective effector functions against many viral, bacterial and parasitic infections. CTL specifically recognize peptides presented by major histocompatibility complex (MHC) class I molecules on the surface of cells. Usually, CTL are stimulated by peptides from intracellularly synthesized, 'endogenous' protein antigens processed in the cytosol or endoplasmic reticulum. Because of this 'endogenous' processing pathway, immunization with 'exogenous' proteins rarely induces class I-restricted CTL responses. We have found that immunization of mice without adjuvants with a single low dose of, either different lipoprotein particles, or various denatured protein antigens by various routes efficiently primes class I-restricted CTL responses of defined epitope and restriction specificity. Priming of CTL requires processing of S-protein and is not inducible by the respective immunogenic peptides. These data reveal a novel immunogenic property of these two types of 'exogenous' protein antigens. The observation is relevant for the development of subunit vaccines designed to specifically stimulate T cell responses.