Comparison of the Jβ gene usage among different T cell receptor Vβ families in spleens of C57BL/6 mice

Kato, Tomohiro; Suzuki, Satoshi; Sasakawa, Hiroko; Masuko, Kayo; Ikeda, Yoko; Nishioka, Kusuki; Yamamoto, Kazuhiko

doi:10.1002/eji.1830241022

Cited by 21 publications

(9 citation statements)

References 19 publications

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“…S6A; P = 0.67, Wilcoxon signed-rank test) clonotypes. This observation suggests strongly that Vβ and Jβ frequencies are statistically independent, and is consistent with previous results showing similar Jβ frequencies in murine splenic T cells carrying a subset of different Vβ genes (19). The observed independence requires that the frequency of a particular Vβ paired with Dβ1 is not significantly different from the frequency of the same Vβ paired with Dβ2, which is supported by our data (SI Appendix, Fig.…”

Section: Resultssupporting

confidence: 93%

Chromatin conformation governs T-cell receptor Jβ gene segment usage

Ndifon

Gal

Shifrut

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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T cells play fundamental roles in adaptive immunity, relying on a diverse repertoire of T-cell receptor (TCR) α and β chains. Diversity of the TCR β chain is generated in part by a random yet intrinsically biased combinatorial rearrangement of variable (Vβ), diversity (Dβ), and joining (Jβ) gene segments. The mechanisms that determine biases in gene segment use remain unclear. Here we show, using a high-throughput TCR sequencing approach, that a physical model of chromatin conformation at the DJβ genomic locus explains more than 80% of the biases in Jβ use that we measured in murine T cells. This model also predicts correctly how differences in intersegment genomic distances between humans and mice translate into differences in Jβ bias between TCR repertoires of these two species. As a consequence of these structural and other biases, TCR sequences are produced with different a priori frequencies, thus affecting their probability of becoming public TCRs that are shared among individuals. Surprisingly, we find that many more TCR sequences are shared among all five mice we studied than among only subgroups of three or four mice. We derive a necessary mathematical condition explaining this finding, which indicates that the TCR repertoire contains a core set of receptor sequences that are highly abundant among individuals, if their a priori probability of being produced by the recombination process is higher than a defined threshold. Our results provide evidence for an expanded role of chromatin conformation in VDJ rearrangement, from control of gene accessibility to precise determination of gene segment use.lymphocyte receptor repertoires | public T-cell clones | VDJ recombination | epigenetics | next generation sequencing

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Section: Resultssupporting

confidence: 93%

Chromatin conformation governs T-cell receptor Jβ gene segment usage

Ndifon

Gal

Shifrut

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Primers were designed de novo or derived from previous reports (24). The following sequences were used: 5′-GGGGACAAAGAGGTCAAATC-3′ (mTRBV1), 5′-ACCAGGGAC-ACGACTCACCGTCC-3′ (mTRBJ2.1), 5′-GCTCAGATGCCCAATCAGTCGCA-3′ (mTRBV16) and 5′-CCAGGCACTCGGCTCCTCGT-3′ (mTRBJ2.5).…”

Section: A G T G C a G G G A A C T A T A G T G C G G G A A A C T A T mentioning

confidence: 99%

Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoire

Quigley

Greenaway

Venturi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

125

127

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Adaptive T-cell immunity relies on the recruitment of antigenspecific clonotypes, each defined by the expression of a distinct T-cell receptor (TCR), from an array of naïve T-cell precursors. Despite the enormous clonotypic diversity that resides within the naïve T-cell pool, interindividual sharing of TCR sequences has been observed within mobilized T-cell responses specific for certain peptide-major histocompatibility complex (pMHC) antigens. The mechanisms that underlie this phenomenon have not been fully elucidated, however. A mechanism of convergent recombination has been proposed to account for the occurrence of shared, or "public," TCRs in specific memory T-cell populations. According to this model, TCR sharing between individuals is directly related to TCR production frequency; this, in turn, is determined on a probabilistic basis by the relative generation efficiency of particular nucleotide and amino acid sequences during the recombination process. Here, we tested the key predictions of convergent recombination in a comprehensive evaluation of the naïve CD8 + TCRβ repertoire in mice. Within defined segments of the naïve CD8 + T-cell repertoire, TCRβ sequences with convergent features were (i) present at higher copy numbers within individual mice and (ii) shared between individual mice. Thus, the naïve CD8 + T-cell repertoire is not flat, but comprises a hierarchy of recurrence rates for individual clonotypes that is determined by relative production frequencies. These findings provide a framework for understanding the early mobilization of public CD8 + T-cell clonotypes, which can exert profound biological effects during acute infectious processes.

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“…3 for all categories of mice. The BJ1.2 usage was derived from Kato et al (44) and Candeias et al (45). The size of the CD8 ϩ T cell repertoire was calculated as follows: Number of distinct CDR3 sequences found in given peak ϫ 1/percentage of a given CDR3 length peak in a defined BV-BJ1.2 (to correct for all CDR3 peaks present in a single BV-BJ1.2 rearrangement) ϫ 1/percentage of the BV studied (to correct for all Bvs) ϫ 100/5 (to correct for all BJs since BJ1.2 was used in 5% of the rearrangements).…”

Section: Discussionmentioning

confidence: 99%

“…3. The BJ1.2 usage was derived from Kato et al (44). c The percentage of BV-BJ rearrangements bearing the indicated CDR3␤ length was calculated from the Immunoscope profile.…”

Section: Discussionmentioning

confidence: 99%

Vβ T Cell Repertoire of CD8+ Splenocytes Selected on Nonpolymorphic MHC Class I Molecules

Laouini

Casrouge

Dalle

et al. 2000

The Journal of Immunology

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In this work, we have studied the role of the MHC class Ib molecules in the selection and maintenance of CD8+ T splenocytes. We have compared the CD8+ T cell repertoires of wild-type, H-2K-deficient, H-2D-deficient, or double knockout C57BL/6 mice. We show that the different CD8+ repertoires, selected either by class Ia and class Ib or by class Ib molecules only, use the various Vα (AV) and Vβ (BV) rearrangements in the same proportion and without biases in the CDR3 size distribution. Furthermore, we have estimated the size of the BV repertoire in the four different strains of mice. Interestingly, we have found that the BV repertoire size is proportional to the overall number of CD8+ splenocytes. This observation implies that BV diversity is positively correlated with the number of CD8+ cells, even when the number of CD8+ splenocytes is dramatically reduced (90% in the double knockout mice).

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Comparison of the Jβ gene usage among different T cell receptor Vβ families in spleens of C57BL/6 mice

Cited by 21 publications

References 19 publications

Chromatin conformation governs T-cell receptor Jβ gene segment usage

Chromatin conformation governs T-cell receptor Jβ gene segment usage

Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoire

Vβ T Cell Repertoire of CD8+ Splenocytes Selected on Nonpolymorphic MHC Class I Molecules

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