CTL responses to H2-M3-restricted Listeria epitopes.

Cytotoxic T cells (CTL) play a critical role in the murine immune response to Listeria monocytogenes (Listeria). Bacterial antigens are presented to Listeria-specific CTL by products of both conventional, polymorphic MHC class Ia and non-polymorphic MHC class Ib alleles. The H2-M3 class Ib gene product, M3, preferentially presents formylmethionine-initiating (fMet) peptides derived from the N termini of bacterial and mitochondrial proteins. Thus, M3 signals the presence of bacterial invaders to CTL effectors. Listeria-encoded fMet peptide epitopes for H2-M3-restricted CTL have recently been identified. These and other identified fMet peptides are predominantly comprised of hydrophobic residues and appear to be cleaved from membrane-bound proteins. The subcellular location and membrane topology of such proteins may be significant factors in their selection as target antigens for H2-M3-restricted CTL. Such rules may prove useful for prediction of candidate fMet peptide epitopes from other bacterial proteins and species. Studies using synthetic fMet peptides to stimulate CTL ex vivo are also discussed. These latter studies indicate that Listeria infection boosts H2-M3-restricted CTL responses. However, in contrast to MHC class Ia-restricted CTL responses, fMet peptide-specific CTL are observed in a large proportion of cultures from non-immunized, conventionally housed (non-SPF) mice. The CTL activity in these latter cultures may reflect priming in vivo on cross-reactive antigens, or may indicate that requirements for priming of H2-M3-restricted CTL are less stringent than for class Ia-restricted responses.