Permissive recognition of a mycobacterial T-cell epitope: Localization of overlapping epitope core sequences recognized in association with multiple major histocompatibility complex class II I-A molecules

D. P. Harris*, H. M. Vordermeier, A. Arya, C. Moreno, J. Ivanyi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Most T-cell epitopes are recognized in the context of a single or limited number of major histocompatibility complex (MHC) class II molecules. We have shown previously, however, that the immunodominant p61-80 epitope from the Mycobacterium tuberculosis 19,000 MW protein is recognized in a genetically permissive manner. In this study, permissive recognition of p61-80 was analysed in three murine MHC haplotypes (H-2(b,d) and (k)) with respect to: (i) T-cell-epitope core structure; (ii) I-A/I-E class II MHC restriction; and (iii) the identification of critical amino acid residues within the core region. Overlapping epitope core sequences composed of 6 to 8 amino acids were identified for each of the three H-2 haplotypes by T-cell epitope scanning (PEPSCAN) using peptide-specific T-cell lines. The epitope core sequences recognized by peptide and 19,000 MW protein-specific T cells were similar. In all three haplotypes, responses to p61-80 were restricted by class II MHC I-A molecules. To identify residues within the epitope core critically required for recognition, single substitution (alanine or leucine) analogue peptides were tested for their capacity to stimulate p61-80-specific T-cell hybridomas. A heterogeneous pattern of reactivity was observed, even among individual hybridomas derived from the same H-2 haplotype. Although every core residue could be defined as critical for at least one hybridoma, only one critical substitution (74Val→Ala) was common to all hybridomas. The identification and structural analysis of genetically permissive epitopes of mycobacteria may be a useful strategy for the rational design of peptide-based vaccines for tuberculosis.

Original languageEnglish
Pages (from-to)555-561
Number of pages7
JournalImmunology
Volume84
Issue number4
Publication statusPublished - Apr 1995

Keywords

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial/immunology
  • Female
  • H-2 Antigens/immunology
  • Histocompatibility Antigens Class II/immunology
  • Immunization
  • Immunodominant Epitopes/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mycobacterium tuberculosis/immunology
  • Peptide Fragments/immunology
  • T-Lymphocytes/immunology

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