The nature of the immunogen determines the specificity of antibodies and T cells to selected peptides of the 38 kDa mycobacterial antigen.
We report in this study that the nature of the injected immunogen or infection of mice can change the specificity of antibodies against different epitopes of the mycobacterial 38 kDa antigen. Following immunization with a selection of 14 peptides, only p65-83 and p285-304 resulted in antibodies binding to the whole antigen, whereas the recombinant antigen induced antibodies to p201-220 and p230-249, which are non-immunogenic following peptide immunization. Killed tubercle bacilli stimulated antibodies exclusively against the N-terminal 1-20 peptide, whilst infection with live tubercle bacilli led to antibodies recognizing non-continuous epitopes, demonstrable by binding to the 38 kDa protein, but to none of the tested peptides. The most striking finding is that protein immunization failed to induce antibodies to p65-83, although this epitope is immunodominant for T cells, irrespective of the mode of sensitization. Since this peptide contains non-overlapping B (69-75) and T (75-81) cell stimulatory cores, it appears that T help dedicated to the adjacent B epitope following peptide immunization may have shifted in favour of B cells reacting either with distantly located linear epitopes p1-20 and p201-220 following immunization with the whole protein, or to conformational epitopes following tuberculous infection of mice. The mechanisms which can deviate T help from one to another B cell specificity could involve regulation of antigen processing, liable to the nature of the immunogen. The described results suggesting distinct functional pairing between T and B epitopes, but with limited fidelity, may have general implications for the design of subunit vaccines.
Vordermeier
H M
HM
Tuberculosis & Related Infections Unit, MRC Clinical Sciences Centre, London, UK.
Harris
D P
DP
Moreno
C
C
Singh
M
M
Ivanyi
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D010455:Peptides; D011994:Recombinant Proteins; C065517:protein antigen b, Mycobacterium