Abstract:
:Chronic beryllium disease (CBD) is a granulomatous lung disorder that is associated with the accumulation of beryllium (Be)-specific CD4(+) T cells into the lung. Genetic susceptibility is linked to HLA-DPB1 alleles that possess a glutamic acid at position 69 (βGlu69), and HLA-DPB1*02:01 is the most prevalent βGlu69-containing allele. Using HLA-DP2 transgenic (Tg) mice, we developed a model of CBD that replicates the major features of the human disease. Here we characterized the T-cell receptor (TCR) repertoire of Be-responsive CD4(+) T cells derived from the lungs of Be oxide-exposed HLA-DP2 Tg mice. The majority of Be-specific T-cell hybridomas expressed TCR Vβ6, and a subset of these hybridomas expressed identical or nearly identical β-chains that were paired with different α-chains. We delineated mimotopes that bind to HLA-DP2 and form a complex recognized by Be-specific CD4(+) T cells in the absence of Be. These Be-independent peptides possess an arginine at p5 and a tryptophan at p7 that surround the Be-binding site within the HLA-DP2 acidic pocket and likely induce charge and conformational changes that mimic those induced by the Be(2+) cation. Collectively, these data highlight the interplay between peptides and Be in the generation of an adaptive immune response in metal-induced hypersensitivity.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Falta MT,Tinega AN,Mack DG,Bowerman NA,Crawford F,Kappler JW,Pinilla C,Fontenot APdoi
10.1038/mi.2015.54subject
Has Abstractpub_date
2016-01-01 00:00:00pages
218-28issue
1eissn
1933-0219issn
1935-3456pii
mi201554journal_volume
9pub_type
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