H2-M3 Restricted Presentation of a Listeria-derived Leader Peptide

doi:10.1084/jem.187.10.1711

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J. Exp. Med., Volume 187, Number 10, May 18, 1998 1711-1719

H2-M3 Restricted Presentation of a Listeria-derived Leader Peptide

By Michael F. Princiotta,^* Laurel L. Lenz, Michael J. Bevan, and Uwe D. Staerz^*

From the ^* National Jewish Medical and Research Center and Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206; and the Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195

Protective immunity to infection by many intracellular pathogens requires recognition by cytotoxic T lymphocytes (CTLs) ofantigens presented on major histocompatibility complex (MHC) classI molecules. To be presented for recognition by pathogen-specificCTLs, these antigens must gain access to the host cell class Iprocessing pathway. In the case of intracellular bacterial pathogens,the majority of bacterial proteins are retained within the bacterialmembrane and therefore remain inaccessible to the host cell forantigen processing. We have isolated a CTL clone from a C57BL/6mouse infected with the intracellular gram-positive bacteriumListeria monocytogenes (LM) and have identified the source ofthe antigen. Using a genomic expression library, we determinedthat the clone recognizes an antigenic N-formyl peptide presentedby the nonpolymorphic murine MHC class Ib molecule, H2-M3. Severallengths of this peptide were able to sensitize cells for lysisby this CTL clone. The source of this antigenic peptide is a 23-aminoacid polypeptide encoded at the start of a polycistronic region.Analysis of mRNA secondary structure of this region suggests thatthis polypeptide may be a leader peptide encoded by a transcriptionalattenuator.

Key words: Listeria; H2-M3; cytotoxic T lymphocyte; antigen; leader peptide

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