Mapping of melanin-concentrating hormone receptor 1 B cell epitopes predicts two major binding sites for vitiligo patient autoantibodies

Exp Dermatol. 2009 May;18(5):454-63. doi: 10.1111/j.1600-0625.2008.00813.x. Epub 2009 Mar 6.

Abstract

The melanin-concentrating hormone receptor 1 (MCHR1) has been identified as a B cell autoantigen in vitiligo with antibodies to the receptor detectable in binding and function-blocking assays. Two epitope domains (amino acids 1-138 and 139-298) have been previously identified. In this study, we aimed to further define the epitope specificity of MCHR1 antibodies using phage-display technology and to identify the epitopes recognised by receptor antibodies detected in MCHR1 function-blocking assays. Antibody reactivity to MCHR1 peptides 51-80, 85-98, 154-158 and 254-260 was identified by phage-display and subsequently confirmed in phage ELISA in 2/12, 5/12, 3/12 and 6/12 of vitiligo patients, respectively. The results suggest that major autoantibody epitopes are localised in the 85-98 and 254-260 amino acid regions of MCHR1 with minor epitopes in amino acid sequences 51-80 and 154-158. Antibodies with MCHR1 function-blocking activity were determined to recognise epitope 254-260, this being the first epitope to be reported as a target site for antibodies that block the function of the receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / chemistry*
  • Autoantigens / chemistry*
  • Autoimmune Diseases / immunology
  • Binding Sites
  • Biotinylation
  • Epitopes, B-Lymphocyte / chemistry
  • Female
  • Humans
  • Immunoglobulin G / chemistry
  • Male
  • Middle Aged
  • Peptide Library
  • Receptors, Pituitary Hormone / biosynthesis*
  • Receptors, Pituitary Hormone / chemistry*
  • Vitiligo / immunology*
  • Vitiligo / metabolism

Substances

  • Autoantibodies
  • Autoantigens
  • Epitopes, B-Lymphocyte
  • Immunoglobulin G
  • Peptide Library
  • Receptors, Pituitary Hormone
  • melanin-concentrating hormone receptor