TCRβ Feedback Signals Inhibit the Coupling of Recombinationally Accessible Vβ14 Segments with DJβ Complexes

被引：15

作者：

Yang-Iott, Katherine S. ^{[1
,2
,3
]}

Carpenter, Andrea C. ^{[1
,2
,3
,4
]}

Rowh, Marta A. W. ^{[1
,2
,3
,4
]}

Steinel, Natalie ^{[1
,2
,3
,4
]}

Brady, Brenna L. ^{[1
,2
,3
,4
]}

Hochedlinger, Konrad ^{[5
,6
]}

Jaenisch, Rudolf ^{[7
]}

Bassing, Craig H. ^{[1
,2
,3
,4
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Immunol Grad Grp, Philadelphia, PA 19104 USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02114 USA

[6] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA

[7] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 03期

关键词：

CELL-RECEPTOR-BETA; CHROMOSOMAL V(D)J RECOMBINATION; ALLELIC EXCLUSION; V-BETA; GERMLINE TRANSCRIPTION; TRANSGENIC MICE; DEFICIENT MICE; GENE SEGMENT; IMMATURE THYMOCYTES; ANTIGEN RECEPTOR;

D O I：

10.4049/jimmunol.0900723

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Ag receptor allelic exclusion is thought to occur through monoallelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into V beta 14 (V beta 14(Rep)) indicated that V beta 14 chromatin accessibility is biallelic. To determine whether V beta 14 recombinational accessibility is subject to feedback inhibition, we analyzed TCR beta rearrangements in V beta 14(Rep) mice containing a preassembled in-frame transgenic V beta 8.2D beta 1J beta 1.1 or an endogenous V beta 14D beta 1J beta 1.4 rearrangement on the homologous chromosome. Expression of either preassembled V beta DJ beta C beta-chain accelerated thymocyte development because of enhanced cellular selection, demonstrating that the rate-limiting step in early alpha beta T cell development is the assembly of an in-frame V beta DJ beta rearrangement. Expression of these preassembled V beta DJ beta rearrangements inhibited endogenous V beta 14-to-DJ beta rearrangements as expected. However, in contrast to results predicted by the accepted model of TCR beta feedback inhibition, we found that expression of these preassembled TCR beta-chains did not down-regulate recombinational accessibility of V beta 14 chromatin. Our findings suggest that TCR beta-mediated feedback inhibition of V beta 14 rearrangements depends on inherent properties of V beta 14, D beta, and J beta recombination signal sequences. The Journal of Immunology, 2010,184:1369-1378.

引用

页码：1369 / 1378

页数：10

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