MHC class I restricted T cell responses to Listeria monocytogenes, an intracellular bacterial pathogen.
Studies of the murine immune response to infection with the intracellular bacterial pathogen Listeria monocytogenes have provided a wealth of information about innate and acquired immune defenses in the setting of an infectious disease. Our studies have focused on the MHC class I restricted, CD8+ T cell responses of Balb/c mice to L. monocytogenes infection. Four peptides that derive from proteins that L. monocytogenes secretes into the cytosol of infected cells are presented to cytotoxic T lymphocyte (CTL) by the H2-Kd major histocompatibility complex (MHC) class I molecule. We have found that bacterially secreted proteins are rapidly degraded in the host cell cytosol by proteasomes that utilize, at least in part, the N-end rule to determine the rate of degradation. The MHC class I antigen processing pathway is remarkably efficient at generating peptides that bind to MHC class I molecules. The magnitude of in vivo T cell responses, however, is influenced to only a small degree by the amount of antigen or the efficiency of antigen presentation. Measurements of in vivo T cell expansion following L. monocytogenes infection indicate that differences in the sizes of peptide-specific T cell responses are more likely owing to differences in the repertoire of naive T cells than to differences in peptide presentation. This notion is supported by our additional finding that dominant T cell populations express a more diverse T cell receptor (TCR) repertoire than do subdominant T cell populations.
Finelli
A
A
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520-8022, USA.
Kerksiek
K M
KM
Allen
S E
SE
Marshall
N
N
Mercado
R
R
Pilip
I
I
Busch
D H
DH
Pamer
E G
EG
D000818:Animals; D017951:Antigen Presentation; D000939:Epitopes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell