Celiac.com 02/18/2015 - It's well documented that HLA-DQ molecules play a role in the pathogenesis of celiac disease through the presentation of gluten peptides to CD4(+) T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease.
Researchers have recently showed that T cells of DQ2.5 and DQ2.2 patients recognize distinct sets of gluten epitopes, which indicates that these two DQ2 variants select different peptides for display.
The team began by isolating peptides from affinity-purified HLA molecules of nine cell lines. They then subjected the isolated peptides to quadrupole orbitrap mass spectrometry and MaxQuant software analysis. They identified 12,712 endogenous peptides at very different relative abundances. Hierarchical clustering of normalized quantitative data revealed significant differences in repertoires of peptides between the three DQ variant molecules.
They identified peptide-binding motifs using the neural network-based method, NNAlign. The binding motifs of DQ2.5 and DQ7.5 concurred with previously established binding motifs, but the binding motif of DQ2.2 was remarkably different from that of DQ2.5, with position, P3 being a major anchor having a preference for threonine and serine.
This is interesting for the reason that three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine at position P3.
This study shows that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules can provide clues to understand HLA association with disease.