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Quantitative tracking of T cell clones after haematopoietic stem cell transplantation.

Mamedov IZ, Britanova OV, Bolotin DA, Chkalina AV, Staroverov DB, Zvyagin IV, Kotlobay AA, Turchaninova MA, Fedorenko DA, Novik AA, Sharonov GV, Lukyanov S, Chudakov DM, Lebedev YB - EMBO Mol Med (2011)

Bottom Line: Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood.Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use it to perform the first detailed, quantitative tracking of T cell clones during 10 months after transplantation.We show that multiple clones survive the procedure, contribute to the immune response to activated infections, and form a new skewed and stable T cell receptor repertoire.

View Article: PubMed Central - PubMed

Affiliation: Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.

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Related in: MedlinePlus

In silico CDR3 region spectratyping and clonotyping of selected TCR V beta gene segments before, 4 months after, and 10 months after HSCTCDR3 length is plotted along the x-axis. The 3 clones that were most abundant in at least one of the 3 blood samples are shown by individual colours. The abundance of the clonal TCR beta sequence, expressed as a percentage of total TCR beta sequences is plotted on the y-axis. Percentage of the clonal sequence among all sequences carrying the same TCR V beta gene is shown in pie graphs. CMV-specific clones CASSLAPGATNEKLFF-1 and -2 identified by MHC tetramer assay are shown in bold.TCR V beta 12-4TCR V beta 7-9TCR V beta 7-6TCR V beta 9
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fig02: In silico CDR3 region spectratyping and clonotyping of selected TCR V beta gene segments before, 4 months after, and 10 months after HSCTCDR3 length is plotted along the x-axis. The 3 clones that were most abundant in at least one of the 3 blood samples are shown by individual colours. The abundance of the clonal TCR beta sequence, expressed as a percentage of total TCR beta sequences is plotted on the y-axis. Percentage of the clonal sequence among all sequences carrying the same TCR V beta gene is shown in pie graphs. CMV-specific clones CASSLAPGATNEKLFF-1 and -2 identified by MHC tetramer assay are shown in bold.TCR V beta 12-4TCR V beta 7-9TCR V beta 7-6TCR V beta 9

Mentions: Clones, which survived, established a new balance that was unexpectedly stable, as revealed by in silico analysis, which demonstrates that the spectratypes and clonotypes skewed by HSCT remained intact over the next 6 months (Fig 2). Restoration of a full TCR beta repertoire which would re-produce the previous diversity and the clonal expansions normally present in healthy subjects, would probably take years, especially given the low abundance of naive T cells observed in the patient blood after HSCT (Supporting Information Fig 8).


Quantitative tracking of T cell clones after haematopoietic stem cell transplantation.

Mamedov IZ, Britanova OV, Bolotin DA, Chkalina AV, Staroverov DB, Zvyagin IV, Kotlobay AA, Turchaninova MA, Fedorenko DA, Novik AA, Sharonov GV, Lukyanov S, Chudakov DM, Lebedev YB - EMBO Mol Med (2011)

In silico CDR3 region spectratyping and clonotyping of selected TCR V beta gene segments before, 4 months after, and 10 months after HSCTCDR3 length is plotted along the x-axis. The 3 clones that were most abundant in at least one of the 3 blood samples are shown by individual colours. The abundance of the clonal TCR beta sequence, expressed as a percentage of total TCR beta sequences is plotted on the y-axis. Percentage of the clonal sequence among all sequences carrying the same TCR V beta gene is shown in pie graphs. CMV-specific clones CASSLAPGATNEKLFF-1 and -2 identified by MHC tetramer assay are shown in bold.TCR V beta 12-4TCR V beta 7-9TCR V beta 7-6TCR V beta 9
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377069&req=5

fig02: In silico CDR3 region spectratyping and clonotyping of selected TCR V beta gene segments before, 4 months after, and 10 months after HSCTCDR3 length is plotted along the x-axis. The 3 clones that were most abundant in at least one of the 3 blood samples are shown by individual colours. The abundance of the clonal TCR beta sequence, expressed as a percentage of total TCR beta sequences is plotted on the y-axis. Percentage of the clonal sequence among all sequences carrying the same TCR V beta gene is shown in pie graphs. CMV-specific clones CASSLAPGATNEKLFF-1 and -2 identified by MHC tetramer assay are shown in bold.TCR V beta 12-4TCR V beta 7-9TCR V beta 7-6TCR V beta 9
Mentions: Clones, which survived, established a new balance that was unexpectedly stable, as revealed by in silico analysis, which demonstrates that the spectratypes and clonotypes skewed by HSCT remained intact over the next 6 months (Fig 2). Restoration of a full TCR beta repertoire which would re-produce the previous diversity and the clonal expansions normally present in healthy subjects, would probably take years, especially given the low abundance of naive T cells observed in the patient blood after HSCT (Supporting Information Fig 8).

Bottom Line: Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood.Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use it to perform the first detailed, quantitative tracking of T cell clones during 10 months after transplantation.We show that multiple clones survive the procedure, contribute to the immune response to activated infections, and form a new skewed and stable T cell receptor repertoire.

View Article: PubMed Central - PubMed

Affiliation: Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.

Show MeSH
Related in: MedlinePlus