Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae.
We have used different mouse strains to examine in vivo and in vitro responses to the 18 kDa protein of Mycobacterium leprae, which appears to be strongly immunogenic in both mice and humans. B and T cell stimulatory epitopes recognised by different strains of mice have been mapped using overlapping peptides that span the entire 18 kDa protein. Previous work established that immunization of mice with the 18 kDa protein results in specific antibody production to common B cell epitopes and immunization of mice with peptides containing these B cell epitopes resulted in the induction of specific IgG to only a limited subset of epitopes in each strain. Now we report that T cells purified from mice immunized with peptides that stimulate antibody production, proliferate in vitro when rechallenged. The proliferating T cells produce levels of IL-2 and IFN-gamma, that indicate antigen-specific T helper type 1 cells are present in significant numbers. Thus, a comparison of in vivo and in vitro data suggests that T cells bearing the phenotype associated with potentially protective cell-mediated responses can be primed in vivo by epitopes on small peptides. Since T cells from both strains of mice are capable of responding to the immunogenic synthetic peptides in vitro, but give different responses to the same peptides in vivo, factors other than epitope structure appear to influence T cell subset activation. This may have important implications for diseases such as leprosy where a polarized T cell response appears to develop and for the development of synthetic subunit vaccines.
Doherty
T M
TM
Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand.
Bäckström
B T
BT
Love
S G
SG
Harding
D R
DR
Watson
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000235:genetics / Q000276:immunology*; D010449:Peptide Mapping; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D000939:Epitopes