Promiscuous T cell recognition of an H‐2 IA‐presented mycobacterial epitope

H. Martin Vordermeier, David P. Harris, Carlos Moreno, Juraj Ivanyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Genetically permissive T cell epitopes are an important prerequisite for the development of peptide-based vaccines or immunodiagnostic reagents. We have investigated the structural requirements of permissive T cell recognition of peptide p350-369 from the 38-kDa antigen of Mycobacterium tuberculosis. This peptide was found to be immunogenic in mice of the H-2b, bm12, d, s and k, but not of the H-2f genotype. T cell responses were restricted by I-A class II molecules. The same epitope core was recognized in the H-2b, d and k genotypes. T cell hybrids from BALB/c and C57BL/10 mice were used to determine: (i) the critical residues using substituted peptide derivatives and (ii) the degree of T cell promiscuity. Two out of five BALB/c (H-2d)-derived hybridomas tested displayed promiscuous peptide recognition in the context of H-2b and H-2bm12 antigen-presenting cells. The recognition of critical residues was found to be uniform for all five hybridomas when tested with syngeneic antigen-presenting cells; additional critical residues were identified when the peptide was recognized in the context of allogeneic antigen-presenting cells. Only one of the four tested C57BL/10 (H-2b) hybridomas showed promiscuity in the context of H-2bm12. Each of these C57BL/10-derived clones had a distinct response profile toward the critical residues. We propose that the demonstrated T cell promiscuity involves peptide interaction with polymorphic H-2 I-A residues.

Original languageEnglish
Pages (from-to)2061-2067
Number of pages7
JournalEuropean Journal of Immunology
Volume24
Issue number9
DOIs
Publication statusPublished - 01 Sept 1994

Keywords

  • Class II molecules
  • Major histocompatibiliy complex
  • T cell promiscuity
  • Amino Acid Sequence
  • Mycobacterium tuberculosis/immunology
  • T-Lymphocytes/immunology
  • Molecular Sequence Data
  • Epitopes/chemistry
  • Male
  • Antigen Presentation/immunology
  • Mice, Inbred Strains
  • Haplotypes/genetics
  • Animals
  • Female
  • Mice
  • Antigens, Bacterial/immunology
  • Histocompatibility Antigens Class II/genetics

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