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Abstract
Ankylosing spondylitis (AS) is commonly characterized by clonal expansions of T cells. However, these clonal populations are poorly studied and their role in disease initiation and progression remains unclear. Here, we performed mass sequencing of TCR V beta libraries to search for the expanded T cell clones for two AS patients. A number of clones comprising more than 5% of the corresponding TCR V beta family were identified in both patients. For the first time, expanded clones were shown to be stably abundant in blood samples of AS patients for the prolonged period (1.5 and 2.5 years for two patients, correspondingly). These clones were individually characterized in respect to their differentiation status using fluorescent cell sorting with CD27, CD28, and CD45RA markers followed by quantitative identification of each clone within corresponding fraction using real time PCR analysis. Stable clones differed in phenotype and several were shown to belong to the proinflammatory CD27 − /CD28 − population. Their potentially cytotoxic status was confirmed by staining with perforin-specific antibodies. Search for the TCR V beta CRD3 sequences homologous to the identified clones revealed close matches with the previously reported T cell clones from AS and reactive arthritis patients, thus supporting their role in the disease and proposing consensus TCR V beta CDR3 motifs for AS. Interestingly, these motifs were also found to have homology with earlier reported virus-specific CDR3 variants, indicating that viral infections could play role in development of AS.
Acknowledgements
We thank Ilya Yampolsky and Ekaterina Zvezdova for the help in manuscript preparation. This work was supported by two grants from Molecular and Cell Biology Program RAS for D.M.C. and Y.B.L., by grants from the Howard Hughes Medical Institute (55005618), Rosnauka (02.512.12.2053), “State Support of the Leading Scientific Schools” (NS-2395.2008.4), and Basic Research for Medicine RAS. D.M.C. and I.Z.M. are supported by Grants of the President of Russian Federation (MK-6119.2008.4). Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.