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

:  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 a...

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Bibliographic Details
Published in:Experimental dermatology 2009-05, Vol.18 (5), p.454-463
Main Authors: Gavalas, Nikos G., Gottumukkala, Raju V. S. R. K., Gawkrodger, David J., Watson, Philip F., Weetman, Anthony P., Helen Kemp, E.
Format: Article
Language:English
Subjects:
Adult
Autoantibodies - chemistry
autoantibody
autoantigen
Autoantigens - chemistry
Autoimmune Diseases - immunology
Binding Sites
Biological and medical sciences
Biotinylation
Dermatology
epitope
Epitopes, B-Lymphocyte - chemistry
Female
Humans
Immunoglobulin G - chemistry
Male
Medical sciences
melanin-concentrating hormone receptor 1
Middle Aged
Peptide Library
Pigmentary diseases of the skin
Receptors, Pituitary Hormone - biosynthesis
Receptors, Pituitary Hormone - chemistry
vitiligo
Vitiligo - immunology
Vitiligo - metabolism
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Summary::  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.
ISSN:0906-6705
1600-0625
DOI:10.1111/j.1600-0625.2008.00813.x