Processing of Listeria monocytogenes antigens and the in vivo T-cell response to bacterial infection.
Presentation of antigens to T lymphocytes is a critical step in the clearance of pathogens from their hosts and in the establishment of protective immunity. Several animal models have been developed to study this process, but few have been as informative as the murine immune response to Listeria monocytogenes infection. Herein we review the presentation of L. monocytogenes proteins by the MHC class I antigen-processing pathway and the in vivo T-cell response to these bacterial antigens. These studies demonstrate the following: 1) The size of a peptide-specific T-cell response does not correlate with the amount of epitope presented by infected cells; 2) T cells specific for dominant epitopes do not, in the case of L. monocytogenes infection, inhibit responses to subdominant epitopes; 3) T cells responding to different epitopes presented by MHC class Ia molecules expand, contract and enter the memory pool synchronously; 4) Repeated in vivo expansion of antigen-specific T-cell populations results in a narrowing of their T-cell receptor repertoire and in an increase in their affinity for antigen; and 5) T cells restricted by H2-M3 MHC class Ib molecules constitute a major part of the primary response to bacterial infection, but appear to play a relatively smaller role in memory responses. These studies have provided a novel glimpse of the relationship between antigen processing and in vivo T-cell responses to infection, and provide a foundation for more detailed analyses of T-cell mediated adaptive immunity.
Busch
D H
DH
Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut 06520-8022, USA.
Kerksiek
K
K
Pamer
E G
EG
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II