Peptides presented by HLA-DR molecules in synovia of patients
with rheumatoid,arthritis or antibiotic-refractory Lyme arthritis.
Mol Cell Proteomics. 2010 Nov 16; [Epub ahead of print]
Peptides presented by HLA-DR molecules in synovia of patients with
rheumatoid arthritis or antibiotic-refractory Lyme arthritis.
Seward RJ, Drouin EE, Steere AC, Costello CE.
Boston Univ School of Medicine, United States;
Disease-associated HLA-DR molecules, which may present autoantigens,
constitute the greatest genetic risk factor for rheumatoid arthritis (RA)
and antibiotic-refractory Lyme arthritis (LA). The peptides presented by
HLA-DR molecules in synovia have not previously been defined. Using tandem
mass spectrometry, rigorous database searches and manual spectral
interpretation, we identified 1,427 HLA-DR-presented peptides (220 to 464
per patient) from the synovia of four patients, two diagnosed with RA and
two with LA. The peptides were derived from 166 source proteins, including
a
wide range of intracellular and plasma proteins. A few epitopes were found
only in RA or LA patients.
However, two patients with different diseases, who had the same HLA allele,
had the largest number of epitopes in common. In one RA patient, peptides
were identified as originating from source proteins that have been reported
to undergo citrullination under other circumstances, yet neither this
post-translational modification nor anti-CCP antibodies were detected.
Instead, peptides with the post-translational modification of
S-cysteinylation were identified. We conclude that a wide range of proteins
enter the HLA-DR pathway of antigen presenting cells in the patients'
synovial tissue, and their HLA-DR genotype, not the disease-type, appears
to
be the primary determinant of their HLA-DR-peptide repertoire. New insights
into the naturally presented HLA-DR-epitope repertoire in target tissues
may
allow the identification of pathogenic T-cell epitopes, and this could lead
to innovative therapeutic interventions.
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=210
81667&retmode=ref&cmd=prlinks
PMID: 21081667 [PubMed - as supplied by publisher]
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