Promiscuous T cell recognition of an H-2 IA-presented mycobacterial epitope.
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.
Vordermeier
H M
HM
MRC Clinical Sciences Centre, Tuberculosis and Related Infections Unit, Hammersmith Hospital, London, GB.
Harris
D P
DP
Moreno
C
C
Ivanyi
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D000939:Epitopes; D000949:Histocompatibility Antigens Class II