Peptide mimotopes of Mycobacterium tuberculosis carbohydrate immunodeterminants.
Cell-surface saccharides of Mycobacterium tuberculosis appear to be crucial factors in tuberculosis pathogenicity and could be useful antigens in tuberculosis immunodiagnosis. In the present study, we report the successful antigenic and immunogenic mimicry of mannose-containing cell-wall compounds of M. tuberculosis by dodecamer peptides identified by phage-display technology. Using a rabbit antiserum raised against M. tuberculosis cell-surface saccharides as a target for biopanning, peptides with three different consensus sequences were identified. Phage-displayed and chemically synthesized peptides bound to the anticarbohydrate antiserum. Rabbit antibodies elicited against the peptide QEPLMGTVPIRAGGGS recognize the mannosylated M. tuberculosis cell-wall antigens arabinomannan and lipoarabinomannan, and the glycosylated recombinant protein alanine/proline-rich antigen. Furthermore, antibodies were also able to react with mannan from Saccharomyces cerevisiae, but not with phosphatidylinositol dimannosides or arabinogalactan from mycobacteria. These results suggest that the immunogenic peptide mimics oligomannosidic epitopes. Interestingly, this report provides evidence that, in contrast with previously known carbohydrate mimotopes, no aromatic residues are necessary in a peptide sequence for mimicking unusual glycoconjugates synthesized by mycobacteria. The possible usefulness of the identified peptide mimotopes as surrogate reagents for immunodiagnosis and for the study of functional roles of the native non-peptide epitopes is discussed.
Gevorkian
Goar
G
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apdo. Postal 70-228, Coyoacán 04510, Mexico.
Segura
Erika
E
Acero
Gonzalo
G
Palma
José P
JP
Espitia
Clara
C
Manoutcharian
Karen
K
López-Marín
Luz M
LM
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011817:Rabbits
D000907:Antibodies, Bacterial; D000939:Epitopes; D019151:Peptide Library; D010455:Peptides; D011135:Polysaccharides, Bacterial