Induction of M3-restricted cytotoxic T lymphocyte responses by N-formylated peptides derived from Mycobacterium tuberculosis.
Major histocompatibility complex (MHC) class I-restricted CD8(+) T cells play a critical role in the protective immunity against Mycobacterium tuberculosis (Mtb). However, only a few Mtb peptides recognized by MHC class Ia-restricted CD8(+) T cells have been identified. Information on epitopes recognized by class Ib-restricted T cells is even more limited. M3 is an MHC class Ib molecule that preferentially presents N-formylated peptides to CD8(+) T cells. Because bacteria initiate protein synthesis with N-formyl methionine, the unique binding specificity of M3 makes it especially suitable for presenting these particular bacterial epitopes. We have scanned the full sequence of the Mtb genome for NH2-terminal peptides that share features with other M3-binding peptides. Synthetic peptides corresponding to these sequences were tested for their ability to bind to M3 in an immunofluorescence-based peptide-binding assay. Four of the N-formylated Mtb peptides were able to elicit cytotoxic T lymphocytes (CTLs) from mice immunized with peptide-coated splenocytes. The Mtb peptide-specific, M3-restricted CTLs lysed the Mtb-infected macrophages effectively, suggesting that these N-formylated Mtb peptides are presented as the naturally processed epitopes by Mtb-infected cells. Furthermore, T cells from Mtb-infected lungs, spleen, and lymph nodes responded to N-formylated Mtb peptides in an M3-restricted manner. Taken together, our data suggest that M3-restricted T cells may participate in the immune response to Mtb.
Chun
T
T
Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology and Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA.
Serbina
N V
NV
Nolt
D
D
Wang
B
B
Chiu
N M
NM
Flynn
J L
JL
Wang
C R
CR
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D016680:Genome, Bacterial; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009239:N-Formylmethionine / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D009239:N-Formylmethionine; D007371:Interferon-gamma