H2-M3 RESTRICTED PRESENTATION OF A LISTERIA-DERIVED LEADER PEPTIDE

Protective immunity to infection by many intracellular pathogens requi res recognition by cytotoxic T lymphocytes (CTLs) of antigens presente d on major histocompatibility complex (MHC) class I molecules. To be p resented for recognition by pathogen-specific CTLs, these antigens mus t gain access to the host cell class I processing pathway. In the case of intracellular bacterial pathogens, the majority of bacterial prote ins are retained within the bacterial membrane and therefore remain in accessible to the host cell. for antigen processing. We have isolated a CTL clone from a C57BL/6 mouse infected with the intracellular gram- positive bacterium Listeria monocytogenes (LM) and have identified the source of the antigen. Using a genomic expression library, we determi ned that the clone recognizes an antigenic N-formyl peptide presented by the nonpolymorphic murine MHC class Ib molecule, H2-M3. Several len gths of this peptide were able to sensitize cells for lysis by this CT L clone. The source of this antigenic peptide is a 23-amino acid polyp eptide encoded at the start of a polycistronic region. Analysis of mRN A secondary structure of this region suggests that this polypeptide ma y be a leader peptide encoded by a transcriptional attenuator.