TY - JOUR
T1 - Mutagenesis of an immunodominant T cell epitope can affect recognition of different T and B determinants within the same antigen
AU - Harris, David P.
AU - Hill, Mahmuda
AU - Vordermeier, Hans Martin
AU - Jones, Mick
AU - Hewinson, Glyn
AU - Thangaraj, Harry
AU - Ivanyi, Juraj
PY - 1997/3/31
Y1 - 1997/3/31
N2 - 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.
AB - 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.
KW - Antigenic structure
KW - Mutagenesis
KW - Mycobacteria
KW - Peptides
KW - Proteins
KW - Spleen
KW - Antibody Specificity
KW - Mutagenesis, Site-Directed
KW - T-Lymphocytes/immunology
KW - Antigens, Bacterial/genetics
KW - Mice, Inbred C57BL
KW - Recombinant Fusion Proteins/immunology
KW - Epitopes, B-Lymphocyte/biosynthesis
KW - Epitopes, T-Lymphocyte/genetics
KW - Mycobacterium tuberculosis/genetics
KW - Animals
KW - Bacterial Proteins/genetics
KW - Lymphocyte Activation/genetics
KW - Peptide Fragments/immunology
KW - Hybridomas
KW - Female
KW - Mice
KW - Antibodies, Bacterial/biosynthesis
KW - Immunodominant Epitopes/genetics
UR - http://www.scopus.com/inward/record.url?scp=0030612347&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(97)00041-2
DO - 10.1016/S0161-5890(97)00041-2
M3 - Article
C2 - 9244344
AN - SCOPUS:0030612347
SN - 0161-5890
VL - 34
SP - 315
EP - 322
JO - Molecular Immunology
JF - Molecular Immunology
IS - 4
ER -