The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/5/1711/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1711-1719

Articles

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

Michael F. Princiotta*,{ddagger}, Laurel L. Lenz, Michael J. Bevan, and Uwe D. Staerz*,{ddagger}

From the * National Jewish Medical and Research Center and {ddagger} Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206; and the {ddagger}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) of antigens presented on major histocompatibility complex (MHC) class I molecules. To be presented for recognition by pathogen-specific CTLs, these antigens must gain access to the host cell class I processing pathway. In the case of intracellular bacterial pathogens, the majority of bacterial proteins are retained within the bacterial membrane and therefore remain inaccessible 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 determined that the clone recognizes an antigenic N-formyl peptide presented by the nonpolymorphic murine MHC class Ib molecule, H2-M3. Several lengths of this peptide were able to sensitize cells for lysis by this CTL clone. The source of this antigenic peptide is a 23–amino acid polypeptide encoded at the start of a polycistronic region. Analysis of mRNA secondary structure of this region suggests that this polypeptide may be a leader peptide encoded by a transcriptional attenuator.

Key Words: Listeria • H2-M3 • cytotoxic T lymphocyte • antigen • leader peptide

Address correspondence to Uwe Staerz, Department of Medicine, National Jewish Medical and Research Center, K405, 1400 Jackson St., Denver, CO 80206. Phone: 303-398-1767; Fax: 303-398-1396; E-mail: staerzu{at}njc.org

Abbreviations used: BHI, brain heart infusion broth; CHO, Chinese hamster ovary; LLO, listeriolysin O; LM, Listeria monocytogenes; MOI, multiplicity of infection; ORF, open reading frame; rmu, recombinant murine; sf, serum-free..


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