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T cells play an important role in the onset and progression of systemic lupus erythematosus (SLE), and a bias in T cell receptor beta variable (TRBV) families and complementarity determining region three (CDR3) composition in SLE patients and mouse models have been widely reported.However,the relationship between the composition and variation in the TCR β-chain CDR3 repertoire and SLE has not been established.We used Roche 454 high-throughput sequencing to compare and analyze the thymic and splenic TCR β-chain CDR3 mRNA sequences from MRL/lpr mouse at 1 month of age (disease-free), 3 months of age (disease onset), and 5 months of age (disease progression).The diversity (unique CDR3 frequency) in the thymic TCR β-chain CDR3 repertoire from 3-and 5-month-old mouse was significantly lower than that from 1-month-old mouse,while the splenic repertoire from 5-month-old mouse was less diverse than that from 1-and 3-month-old mouse.The number of highly expanded clones (HEC) in the thymuses of 3-and 5-month-old mouse was higher than that in 1-month-old mouse, while that in the spleens of 5-month-old mouse was higher than the number in 1-and 3-month-old mouse.A higher bias in TRBV13-3 usage was observed in the total thymic and splenic CDR3 productive sequences in MRL/lpr mouse at different ages; a highly biased usage of certain TRBV families was observed at both 3 and 5 months of age in both organs (thymus: TRBV26,TRBV17,and TRBV13-3 ; spleen: TRBV4, TRBV13-1, TRBV13-3, and TRBV26).Restricted usage of TRBJ2-5 in the thymus and TRBJ2-7 in the spleen respectively at 1,3, and 5-month-old ages of MRL/lpr mouse, The overview TRBV gene recombined with each TRBJ gene showed the reduced diversity and complexity of the TCR repertoires from 5-month compared to 3-month or 1-month MRL/lpr mouse.The observed occurrence of high frequency (top 5) CDR3 sequences in thymuses and spleens of MRL/lpr mouse at different ages were inconsistent.High frequency CDR3 sequences in the thymuses and spleens from 5 -month-old mouse accounted for over 1% of the total sequence, but were less than 1% in the 3-and 1-month-old mouse.The average number of inserted bases in the N1 region of high frequency CDR3 sequences from 5-and 3-month-old mouse spleens was significantly higher than that in 1 -month-old mouse (2.21,2.49, and 0.48 for 5-, 3-, and 1-month-old mouse, respectively).For base insertion in the N1 region of high frequency CDR3 sequences in the thymus, the average number in 5-month-old mouse (2.8) was greater than that in 3-(1.52) and 1-month-old (1.68) mouse.The high frequency CDR3 (CASSPGLGYNYAEQFF) in the spleen of 5-month old mouse came from the TRBV14 gene family ,but TRBV gene were very low frequency expression at all other sample of MRL/lpr mouse,A common CDR3 (aa) is present in both the thymic and splenic T cells of MRL/lpr mouse at different ages.The thymic and splenic CDR3 regions of 1-month-old mouse showed a low overlap ratio with no differences in the total productive and unique productive sequences,whereas the CDR3 regions of 3-and 5-month-old mouse showed high overlap ratios,with a total productive overlap ratio that was significantly greater than the unique productive overlap ratio.These results indicate that diversity in the TCR CDR3 repertoire from the thymus and spleen from MRL/lpr mouse significantly decreases with increased age (disease progression).Thymic and splenic T cell analysis from mouse of different ages revealed that a bias in usage of common TRBV and TRBJ families in the TCR CDR3 repertoire and N1 region insertions in the high frequency CDR3s significantly increased with disease progression.Features such as composition of common overlapping CDR3 regions and the frequency of the TRBV pairing with the TRBJ in the different-aged mouse may be closely related to the MRL/lpr anti-self T cell response during onset and progression of disease,which may provide a basis for studying the mechanism of the MRL/lpr anti-self T cell response and tailor an individualized treatment targeting these T cells.