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Updated: Jun 16, 2026
Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
The HLA-B*2705 peptidome
Lilach Ben Dror1, Eilon Barnea, Ilan Beer
1Technion-Israel Institute of Technology, Haifa, Israel.
Objective:
The HLA-B27 allele is strongly associated with the group of inflammatory diseases known as the spondylarthritides (SpA). The aim of this study was to perform a large-scale, direct biochemical analysis of the HLA-B*2705 peptidome in order to identify candidates for mimicry between HLA-B27 peptides derived from cartilage proteins and arthritogenic bacterial sequences and to refine the consensus binding motif of this important allele.
Methods:
The peptides were recovered by recombinant expression of soluble HLA-B27 molecules secreted from cultured chondrocytic cells or HeLa cells. Analysis was based on capillary chromatography and tandem mass spectrometry in combination with stable isotope labeling with amino acids in cell culture or chemical labeling with iTRAQ to enhance the validity of the data.
Results:
Over 1,268 B27 peptides were identified, with 569 of them at high certainty, thus enabling better refinement of the B27 motif. This enabled the prediction of both short peptides and long peptides whose middle residues likely bulge out of the binding groove. Moreover, we identified a number of human B27 peptide sequences derived from human cartilage proteins, some of which are similar to common bacterial sequences.
Conclusion:
The peptides we identified may provide the missing link between bacterial infections and the resulting SpA.
Insights
Researchers analyzed HLA-B27 peptides to find links between bacterial infections and spondylarthritides (SpA). They identified human cartilage peptides similar to bacterial sequences, suggesting a molecular mimicry mechanism in SpA development.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- The HLA-B27 allele is a significant genetic factor associated with spondylarthritides (SpA).
- Understanding the molecular interactions involving HLA-B27 is crucial for elucidating SpA pathogenesis.
- Potential molecular mimicry between self-antigens and microbial antigens is a proposed mechanism in autoimmune diseases.
Purpose of the Study:
- To conduct a comprehensive biochemical analysis of the HLA-B*2705 peptidome.
- To identify potential molecular mimicry between HLA-B27-bound peptides from cartilage proteins and bacterial sequences.
- To refine the binding motif of the HLA-B27 allele.
Main Methods:
- Recombinant expression of soluble HLA-B27 molecules from chondrocytic and HeLa cells.
- Peptide recovery using capillary chromatography and tandem mass spectrometry.
- Stable isotope labeling (SILAC) and iTRAQ chemical labeling for enhanced data accuracy.
Main Results:
- Identification of over 1,268 HLA-B27-bound peptides, with 569 confirmed at high confidence.
- Refinement of the HLA-B27 binding motif, allowing prediction of short and long peptides.
- Discovery of human B27 peptide sequences from cartilage proteins exhibiting similarity to bacterial sequences.
Conclusions:
- The identified peptides may represent the crucial link between bacterial infections and the development of SpA.
- Molecular mimicry involving HLA-B27 and bacterial antigens is a plausible mechanism in SpA pathogenesis.
- This study provides a refined understanding of the HLA-B27 peptidome and its implications for inflammatory diseases.
