Identification of a peptide mimic of the L2/HNK-1 carbohydrate epitope.
The L2/HNK-1 carbohydrate is carried by many neural recognition molecules and is involved in neural cell interactions during development, regeneration in the peripheral nervous system, synaptic plasticity, and autoimmune-based neuropathies. Its key structure consists of a sulfated glucuronic acid linked to lactosaminyl residues. Because of its biological importance but limited availability, the phage display method was used to isolate a collection of peptide mimics that bind specifically to an L2/HNK-1 antibody. The phages isolated from a 15-mer peptide library by adsorption to this antibody share a consensus sequence of amino acids. The peptide mimicked several important functions of the L2/HNK-1 carbohydrate, such as binding to motor neurons in vitro, and preferential promotion of in vitro neurite outgrowth from motor axons compared with sensory neurons. A scrambled version of the peptide had no activity. The combined observations indicate that we have isolated a mimic of the L2/HNK-1 carbohydrate that is able to act as its functional substitute.
Simon-Haldi
Maryline
M
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich, Switzerland.
Mantei
Ned
N
Franke
Jens
J
Voshol
Hans
H
Schachner
Melitta
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology; D001667:Binding, Competitive / Q000502:physiology; D018959:CD57 Antigens / Q000737:chemistry* / Q000276:immunology; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry* / Q000276:immunology; D002478:Cells, Cultured; D002642:Chick Embryo; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology; D018716:Molecular Mimicry / Q000502:physiology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D013379:Substrate Specificity / Q000502:physiology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018959:CD57 Antigens; D002241:Carbohydrates; D000939:Epitopes; D006017:Glycolipids; D019151:Peptide Library; D010455:Peptides