TY - JOUR
T1 - Promiscuous T cell recognition of an H‐2 IA‐presented mycobacterial epitope
AU - Vordermeier, H. Martin
AU - Harris, David P.
AU - Moreno, Carlos
AU - Ivanyi, Juraj
PY - 1994/9/1
Y1 - 1994/9/1
N2 - 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.
AB - 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.
KW - Class II molecules
KW - Major histocompatibiliy complex
KW - T cell promiscuity
KW - Amino Acid Sequence
KW - Mycobacterium tuberculosis/immunology
KW - T-Lymphocytes/immunology
KW - Molecular Sequence Data
KW - Epitopes/chemistry
KW - Male
KW - Antigen Presentation/immunology
KW - Mice, Inbred Strains
KW - Haplotypes/genetics
KW - Animals
KW - Female
KW - Mice
KW - Antigens, Bacterial/immunology
KW - Histocompatibility Antigens Class II/genetics
UR - http://www.scopus.com/inward/record.url?scp=0028023488&partnerID=8YFLogxK
U2 - 10.1002/eji.1830240919
DO - 10.1002/eji.1830240919
M3 - Article
C2 - 7522158
AN - SCOPUS:0028023488
SN - 0014-2980
VL - 24
SP - 2061
EP - 2067
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 9
ER -