Peptides that mimic Candida albicans-derived beta-1,2-linked mannosides.
Beta-1,2-linked mannosides from Candida albicans phosphopeptidomannan (PPM) bind to macrophages through a receptor independent from the macrophage alpha-linked mannose receptor and stimulate these cells to secrete immune mediators. Anti-beta-1,2-linked mannoside but not anti-alpha-linked mannoside antibodies produced after immunization with neoglycoproteins protect animals from disseminated candidiasis. In this study, peptides that mimic beta-1,2-linked mannosides were isolated using phage display methodology. A phage library expressing random peptides was panned with an anti-beta-1,2-linked mannoside monoclonal antibody (mAb). After three rounds of biopanning, the isolated phages were able to inhibit recognition of C. albicans by the mAb. Sixty percent of the phages had an identical DNA insert corresponding to the peptide sequence FHENWPS that was recognized specifically by the mAb. Injection of KLH-coupled peptide into mice generated high titers of polyclonal antibodies against C. albicans yeast cell walls. The anti-FHENWPS antibodies bound to C. albicans PPM and were inhibited by soluble beta-1,2-mannotetraose. Together, these data provide evidence for mimotopic activity of the peptide selected by biopanning with the anti-beta-1,2-oligomannoside mAb.
Jouault
T
T
Laboratoire de Mycologie Fondamentale et Appliquée, INSERM EPI 9915, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, Place Verdun, 59037 Lille Cedex, France.
Fradin
C
C
Dzierszinski
F
F
Borg-Von-Zepelin
M
M
Tomavo
S
S
Corman
R
R
Trinel
P A
PA
Kerckaert
J P
JP
Poulain
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002176:Candida albicans / Q000737:chemistry*; D002236:Carbohydrate Conformation; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D019151:Peptide Library
D000911:Antibodies, Monoclonal; D005656:Fungal Proteins; D009842:Oligopeptides; D009844:Oligosaccharides; D019151:Peptide Library; C028569:oligomannoside