Do Th1 or Th2 sequence motifs exist in proteins? Identification of amphipatic immunomodulatory domains in Helicobacter pylori catalase.
The reasons why some proteins induce a particular type of T helper (Th) response are of fundamental importance but only partially understood. In the present study, amphipatic sequence motifs were identified in N- and C-terminal domains of Helicobacter pylori (Hp) catalase, which are linked to the induction of Th1 or Th2 immune responses, respectively. Alignment of these motifs with other proteins known to induce either Th1 or Th2 responses has lead to the identification of Th1 and Th2 consensus motifs, termed modulotopes. Their immunomodulatory potential was demonstrated by immunisation experiments using recombinant proteins comprising the C-terminal domain of catalase fused with one or several modulotopes and by co-immunisations of C- or N-terminal catalase domains with peptides containing these motifs. In addition to these in vivo data, in vitro assays using Limulus extracts suggested that modulotopes might interfere with responses triggered by danger signals such as LPS. Th1 and Th2 modulotopes are characterised by a specific hydrophobic/hydrophilic pattern, which might be the structural determinant for their activity. Our data suggest that Th1 and/or Th2 motifs may generally exist on proteins, thus offering the possibility of a rational modulation of the immune response.
Guy
Bruno
B
Research Department, Aventis Pasteur, Campus Merieux, 69280 Marcy l'Etoile, France. bruno.guy@aventis.com
Krell
Tino
T
Sanchez
Violette
V
Kennel
Audrey
A
Manin
Catherine
C
Sodoyer
Regis
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002374:Catalase / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016481:Helicobacter Infections / Q000517:prevention & control; D016480:Helicobacter pylori / Q000201:enzymology* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination
D000941:Antigens; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D010455:Peptides; D011994:Recombinant Proteins; D002374:Catalase