Mutagenesis of an immunodominant T cell epitope can affect recognition of different T and B determinants within the same antigen

David P. Harris, Mahmuda Hill, Hans Martin Vordermeier, Mick Jones, Glyn Hewinson, Harry Thangaraj, Juraj Ivanyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (SciVal)

Abstract

The effects of mutagenesis of residues of a major T cell epitope were investigated in order to expand knowledge from synthetic peptides to the naturally processed antigen. The impact of substitutions within the core of the immunodominant p61-80/PT19 mycobacterial epitope was ascertained in respect of this epitope per se, or of a C-terminal (140-159) overlapping T/B epitope and of a conformational B epitope. The core substitution A71L impaired T immunogenicity of the target epitope within the protein, but not in the peptide, whereas the N73A substitution impaired the responses in both instances. Notably, each of these single amino acid mutations abrogated the T but not the B immunogenicity of the C-terminal epitope. Furthermore, mutation of five core residues (71-76) also ablated expression of a monoclonal antibody defined conformational B epitope. In conclusion, immunological analysis of mutated proteins revealed functional associations between topographically distinct antigenic determinants which may account for the previously observed differences in the specificity of immune responses between immunised and infected hosts.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalMolecular Immunology
Volume34
Issue number4
DOIs
Publication statusPublished - 31 Mar 1997

Keywords

  • Antigenic structure
  • Mutagenesis
  • Mycobacteria
  • Peptides
  • Proteins
  • Spleen
  • Antibody Specificity
  • Mutagenesis, Site-Directed
  • T-Lymphocytes/immunology
  • Antigens, Bacterial/genetics
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins/immunology
  • Epitopes, B-Lymphocyte/biosynthesis
  • Epitopes, T-Lymphocyte/genetics
  • Mycobacterium tuberculosis/genetics
  • Animals
  • Bacterial Proteins/genetics
  • Lymphocyte Activation/genetics
  • Peptide Fragments/immunology
  • Hybridomas
  • Female
  • Mice
  • Antibodies, Bacterial/biosynthesis
  • Immunodominant Epitopes/genetics

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