Epitopes described in "Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease."

Article Authors:Michael T Falta; Clemencia Pinilla; Douglas G Mack; Alex N Tinega; Frances Crawford; Marc Giulianotti; Radleigh Santos; Gina M Clayton; Yuxiao Wang; Xuewu Zhang; Lisa A Maier; Philippa Marrack; John W Kappler; Andrew P Fontenot
Article Title:Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease.
Reference Detail
Reference ID:1026715
Abstract:Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4⁺ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4⁺ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4⁺ T cells specific for these ligands in all HLADP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4⁺ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD.
Affiliations:Department of Medicine, University of Colorado, Denver, Aurora, CO 80045, USA.
Reference Type:Literature
PubMed ID:23797096
Journal:J Exp Med
Journal Volume:210
Article Pages:1403-18
Journal ISSN:0022-1007
Article Chemical List:HLA-DP beta-Chains;HLA-DPw2 antigen;Peptide Library;Peptides;Plxna4 protein, human;Receptors, Cell Surface;Beryllium
Article MeSH List:Amino Acid Sequence; Animals; Berylliosis(genetics; immunology; metabolism); Beryllium(immunology; metabolism); Binding Sites; CD4-Positive T-Lymphocytes(immunology); Cell Line; Chronic Disease; HLA-DP beta-Chains(chemistry; genetics; metabolism); Humans; Mice; Peptide Library; Peptides(chemistry; genetics; metabolism); Receptors, Cell Surface(chemistry; genetics; metabolism)
Curation Last Updated:2016-05-11 20:12:11