Genomic organization of the mouse T cell receptor V alpha family.

Jouvin‐Marche, Evelyne; Hue, Isabelle; Marche, Patrice N.; Liebe-Gris, C; Marolleau, Jean‐Pierre; Malissen, Bernard; Cazenave, Pierre-André; Malissen, Marie

doi:10.1002/j.1460-2075.1990.tb07383.x

Cited by 64 publications

(57 citation statements)

References 48 publications

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“…The analysis of AV16, which has two family members, is complicated in that only the sequence of the 3Ј V␣ member has been reported (21,25). Attempts to obtain the sequence of the 5Ј member by genomic PCR did not reveal any novel sequence (data not shown).…”

Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 98%

“…The nomenclature of the V␣ families follows Arden et al (21). AV2 family (oval) has six members in BALB/c mice that are evenly distributed through out the V␣ locus (18,25,31,32). AV16 (21, 25) (rectangle) and AV20 (20, 25) (spade) families both have two known subfamily members mapped to either extreme location.…”

Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 99%

“…AV16 (21, 25) (rectangle) and AV20 (20, 25) (spade) families both have two known subfamily members mapped to either extreme location. AV19 (hexagon) is a single member family located at the very 5Ј end of the V␣ locus (25). The distance between segments did not reflect the actual distance on the V␣ locus.…”

Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 99%

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Ordered and Coordinated Rearrangement of the TCR α Locus: Role of Secondary Rearrangement in Thymic Selection

Huang

Kanagawa

2001

The Journal of Immunology

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The Ag receptor of the T lymphocyte is composed of an αβ heterodimer. Both α- and β-chains are products of the somatic rearrangement of V(D)J segments encoded on the respective loci. During T cell development, β-chain rearrangement precedes α-chain rearrangement. The mechanism of allelic exclusion ensures the expression of a single β-chain in each T cell, whereas a large number of T cells express two functional α-chains. Here we demonstrate evidence that TCR α rearrangement is initiated by rearranging a 3′ Vα segment and a 5′ Jα segment on both chromosomes. Rearrangement then proceeds by using upstream Vα and downstream Jα segments until it is terminated by successful positive selection. This ordered and coordinated rearrangement allows a single thymocyte to sequentially express multiple TCRs with different specificities to optimize the efficiency of positive selection. Thus, the lack of allelic exclusion and TCR α secondary rearrangement play a key role in the formation of a functional T cell repertoire.

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Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 98%

Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 99%

Section: Location-dependent and Coordinated Rearrangement Of V␣/j␣ Sementioning

confidence: 99%

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Ordered and Coordinated Rearrangement of the TCR α Locus: Role of Secondary Rearrangement in Thymic Selection

Huang

Kanagawa

2001

The Journal of Immunology

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“…Between 75 and 100 ADV segments and 60 AJ segments are available for V(D)J recombination in mice (21)(22)(23). Accessibility of the TCR gene segments for V(D)J recombination is controlled in part by enhancer elements located in the TCR loci (reviewed in Refs.…”

mentioning

confidence: 99%

TCRA Gene Rearrangement in Immature Thymocytes in Absence of CD3, Pre-TCR, and TCR Signaling

Mancini

Candéias

Santo

et al. 2001

The Journal of Immunology

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During thymocyte differentiation, TCRA genes are massively rearranged only after productively rearranged TCRB genes are expressed in association with pTα and CD3 complex molecules within a pre-TCR. Signaling from the pre-TCR via the CD3 complex is thought to be required to promote TCRA gene accessibility and recombination. However, αβ+ thymocytes do develop in pTα-deficient mice, showing that TCRα-chain genes are rearranged, either in CD4−CD8− or CD4+CD8+ thymocytes, in the absence of pre-TCR expression. In this study, we analyzed the TCRA gene recombination status of early immature thymocytes in mutant mice with arrested thymocyte development, deficient for either CD3 or pTα and γc expression. ADV genes belonging to different families were found rearranged to multiple AJ segments in both cases. Thus, TCRA gene rearrangement is independent of CD3 and γc signaling. However, CD3 expression was found to play a role in transcription of rearranged TCRα-chain genes in CD4−CD8− thymocytes. Taken together, these results provide new insights into the molecular control of early T cell differentiation.

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“…Wild-type peripheral ␣␤ T lymphocytes have V␣-to-J␣ rearrangements on both alleles, resulting in the placement of TCR␦ genes on extrachromosomal circles that are lost upon cell division (34,35). In contrast, T cells heterozygous for deletion of E␣ exhibit V␣-to-J␣ rearrangement on only the E␣ ϩ allele (19).…”

Section: E␦ Does Not Promote Efficient J␣ Accessibility When Located mentioning

confidence: 99%

T cell receptor (TCR) α/δ locus enhancer identity and position are critical for the assembly of TCR δ and α variable region genes

Bassing

Tillman

Woodman

et al. 2003

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

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T cell receptor (TCR) ␦ and ␣ variable region genes are assembled from germ-line gene segments located in a single chromosomal locus in which TCR␦ segments are situated between TCR␣ segments. The TCR␣ enhancer (E␣) located at the 3 end of the TCR␣͞␦ locus functions over a long chromosomal distance to promote TCR␣ rearrangement and maximal TCR␦ expression; whereas the TCR␦ enhancer (E␦) is located among the TCR␦ segments and functions with additional element(s) to mediate TCR␦ rearrangement. We used gene-targeted mutation to evaluate whether the identity of E␣ and the position of E␦ are critical for the developmental stage-specific assembly of TCR ␦ and ␣ variable region genes. Specific replacement of E␣ with E␦, the core E␣ element (E␣C), or the Ig heavy chain intronic enhancer (iE ), all of which promote accessibility in the context of transgenic V(D)J recombination substrates, did not promote a significant level of TCR␣ rearrangement beyond that observed in the absence of E␣. Therefore, the identity and full complement of E␣-binding sites are critical for promoting accessibility within the TCR␣ locus. In the absence of the endogenous E␦ element, specific replacement of E␣ with E␦ also did not promote TCR␦ rearrangement. However, deletion of intervening TCR␣͞␦ locus sequences to restore the inserted E␦ to its normal chromosomal position relative to 5 sequences rescued TCR␦ rearrangement. Therefore, unlike E␣, E␦ lacks ability to function over the large intervening TCR␣ locus and͞or E␦ function requires proximity to additional upstream element(s) to promote TCR␦ accessibility.T he exons that encode T cell receptor (TCR) and Ig variable regions are assembled during lymphocyte development from component variable (V), diversity (D), and joining (J) gene segments (1, 2). Both ␣␤ and ␥␦ T cells develop from CD4 Ϫ ͞ CD8 Ϫ (double negative, DN) thymocytes in which TCR␤, -␥, and -␦ genes are all assembled (3). Productive VDJ␤ rearrangements generate TCR␤ chains that associate with surrogate TCR␣ chains to form preTCRs that signal expansion and differentiation to the CD4 ϩ ͞CD8 ϩ (double positive, DP) thymocyte stage (4, 5). Functional VJ␣ rearrangements in DP cells generate TCR␣ chains that, when expressed as surface ␣␤ TCR, direct cellular selection and development to the CD4 ϩ or CD8 ϩ (single positive, SP) thymocytes that exit the thymus as mature ␣␤ T cells (6). Alternatively, productive VDJ␦ and VJ␥ rearrangements in DN progenitor (pro-) T cells generate TCR␦ and -␥ chains that form cell surface ␥␦ TCR and direct ␥␦ T cell development (4, 5).The TCR␣͞␦ locus spans 1 Mb and contains variable region gene segments for two distinct antigen receptors (7). The 5Ј end of the locus consists of a cluster of Ϸ90 V␣͞V␦ gene segments with V␦s concentrated near the 3Ј end of the cluster, and the 3Ј end of the locus consists of a cluster of 50 J␣ segments that spans Ϸ60 kb followed by the TCR␣ constant region (C␣). The D␦ (D␦1 and D␦2) and J␦ (J␦1 and J␦2) segments, the TCR␦ constant region (C␦) and V␦5 lie between the V␣͞V␦ and...

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Genomic organization of the mouse T cell receptor V alpha family.

Cited by 64 publications

References 48 publications

Ordered and Coordinated Rearrangement of the TCR α Locus: Role of Secondary Rearrangement in Thymic Selection

Ordered and Coordinated Rearrangement of the TCR α Locus: Role of Secondary Rearrangement in Thymic Selection

TCRA Gene Rearrangement in Immature Thymocytes in Absence of CD3, Pre-TCR, and TCR Signaling

T cell receptor (TCR) α/δ locus enhancer identity and position are critical for the assembly of TCR δ and α variable region genes

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