Induction of M3-restricted cytotoxic T lymphocyte responses by N-formylated peptides derived from Mycobacterium tuberculosis

• Published in: The Journal of experimental medicine Vol. 193; no. 10; pp. 1213 - 1220
• Main Authors: Chun, T, Serbina, N V, Nolt, D, Wang, B, Chiu, N M, Flynn, J L, Wang, C R
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 21.05.2001
• Subjects: Animals; Antigens, Bacterial - immunology; Brief Definitive Report; Genome, Bacterial; Histocompatibility Antigens Class I - immunology; Interferon-gamma - metabolism; Macrophages - immunology; Macrophages - microbiology; Mice; Mycobacterium tuberculosis - immunology; N-Formylmethionine - immunology; Oligopeptides - immunology; Phenotype; T-Lymphocytes, Cytotoxic - immunology; Tuberculosis - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.193.10.1213

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.