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

Taehoon Chun, Natalya V. Serbina, Dawn Nolt, Bin Wang, Nancy M. Chiu, Jo Anne L. Flynn, Chyung Ru Wang

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1213-1220
Number of pages8
JournalJournal of Experimental Medicine
Volume193
Issue number10
DOIs
Publication statusPublished - 2001 May 21

Keywords

  • Infection
  • MHC
  • Mycobacterium tuberculosis
  • N-formylated peptides
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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