Promiscuous T Cell Recognition of an H-2 IA-presented Mycobacterial Epitope

Eur J Immunol. 1994 Sep;24(9):2061-7. doi: 10.1002/eji.1830240919.

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.

MeSH terms

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

Substances

  • Antigens, Bacterial
  • Epitopes
  • Histocompatibility Antigens Class II