Title |
Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis
|
---|---|
Published in |
Frontiers in immunology, November 2016
|
DOI | 10.3389/fimmu.2016.00494 |
Pubmed ID | |
Authors |
Christina Gerstner, Anatoly Dubnovitsky, Charlotta Sandin, Genadiy Kozhukh, Hannes Uchtenhagen, Eddie A. James, Johan Rönnelid, Anders Jimmy Ytterberg, Jennifer Pieper, Evan Reed, Carolina Tandre, Mary Rieck, Roman A. Zubarev, Lars Rönnblom, Tatyana Sandalova, Jane H. Buckner, Adnane Achour, Vivianne Malmström |
Abstract |
Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS) elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Venezuela, Bolivarian Republic of | 1 | 20% |
Unknown | 4 | 80% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 60% |
Scientists | 1 | 20% |
Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Denmark | 1 | 1% |
Unknown | 73 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 16 | 22% |
Researcher | 11 | 15% |
Student > Master | 10 | 14% |
Student > Bachelor | 4 | 5% |
Professor | 3 | 4% |
Other | 8 | 11% |
Unknown | 22 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 15 | 20% |
Agricultural and Biological Sciences | 14 | 19% |
Biochemistry, Genetics and Molecular Biology | 12 | 16% |
Chemistry | 4 | 5% |
Medicine and Dentistry | 4 | 5% |
Other | 2 | 3% |
Unknown | 23 | 31% |