Variable immunodominance hierarchies for H2-M3-restricted N-formyl peptides following bacterial infection.
H2-M3-restricted presentation of N-formyl methionine (f-Met) peptides to CD8(+) T cells provides a mechanism for selective recognition of bacterial infection. In this report we demonstrate that Listeria monocytogenes infection induces distinct CD8(+) T cell populations specific for each of the known Listeria-derived formyl methionine peptides presented by M3. The sum H2-M3-restricted, Listeria-specific T cell response constitutes a major fraction of the total CD8(+) T cell response to primary infection. H2-M3-restricted T cell populations expand synchronously in vivo and achieve peak frequencies approximately 2 days earlier than MHC class Ia-restricted T cell populations. Although cross-recognition of different f-Met peptides by M3-restricted T cells was previously described, costaining of CD8(+) T cells ex vivo with H2-M3 tetramers complexed with different f-Met peptides shows that the majority of Listeria-specific, M3-restricted CD8(+) T cells are peptide specific. In contrast to the highly predictable size and immunodominance hierarchies of MHC class Ia-restricted T cell responses, the magnitudes of T cell responses specific for H2-M3-restricted peptides are remarkably variable between genetically identical mice. Our findings demonstrate that H2-M3-restricted T cell responses are distinct from classically restricted T cell responses to bacterial infection.
Kerksiek
K M
KM
Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Busch
D H
DH
Pamer
E G
EG
D000818:Animals; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009239:N-Formylmethionine; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D017510:Protein Folding; D013045:Species Specificity; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D009239:N-Formylmethionine