Ontogeny of the T-cell antigen receptor within the thymus

Snodgrass, H. Ralph; Kisielow, Paweł; Kiefer, Michael; Steinmetz, Michael; Boehmer, Harald von

doi:10.1038/313592a0

Cited by 236 publications

(103 citation statements)

References 39 publications

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“…None of the suppressor hybridomas displayed any bands that were not present in III/4, indicating that the J/32 cluster is not rearranged. We should add that the restriction pattern observed with BW5147 is different from that described by Snodgrass et al (26), possibly because we used a different subclone of BW5147.…”

Section: T Cell Receptor Ct3 Gene Is Not Rearranged In Tsmentioning

confidence: 92%

“…Therefore, we also used the J15 probe, which is a 900 bp Cla I/Eco RI fragment located ~90 bp downstream of the J/32 locus (26). Using this probe and a Hind III digest, potential rearrangements within the J/32 cluster should be detected (26). Fig.…”

Section: T Cell Receptor Ct3 Gene Is Not Rearranged In Tsmentioning

confidence: 99%

“…The probe used for hybridization was 86T5, which is mainly specific for the constant regions (C/31 and C¢/2) of the T cell receptor/3 chain but also hybridizes with diversity and joining regions D/31 and J/31 (14). Another probe, J15, contains the 900 basepair (bp) fragment located ~90 bp downstream of the J132 cluster (26). Hybridization with s2p-labeled cDNA was done at 42°C in 50% formamide, 5× SSC (0.15 M NaC1, 0.015 M sodium citrate, pH 7.0), 5x Denhardt's, 100/~g/ml denatured herring sperm DNA, and 10% dextran sulfate.…”

Section: Cytotoxic Assay and Cell Linesmentioning

confidence: 99%

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Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes.

Blanckmeister¹,

Yamamoto²,

Davis³

et al. 1985

The Journal of Experimental Medicine

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Since their discovery in 1971 (1, 2), T suppressor (Ts) ~ cells have been the object of numerous studies. Particularly helpful in the characterization of Ts cells was the establishment of cloned T cell lines, such as T cell hybridomas, long-term T cell lines, or transformed T cells (for a survey see 3). A surprisingly large number of Ts subpopulations have been distinguished. Ts and suppressor factors (TsF) derived from them belong either to the inducing arm of the suppressor circuit or to the effector arm that ultimately mediates suppression. They appear to be either antigen specific or nonspecific, H-2 restricted, and heavy chain variable region (VH) restricted or nonrestricted (reviewed in 4-6). Recent advances (7-17) in the molecular and genetic characterization of antigenspecific receptors of T cells, consisting of two chains, a and ~8, have not only revealed some degree of homology to immunoglobulin but also a basic similarity of receptors on T helper cells (Th) and cytotoxic T iymphocytes (Tc). In contrast, the nature of the antigen receptors on Ts remains elusive. The rearrangement of/3 chain genes described for Th and Tc have not been observed in most antigen-specific Ts cells (18), suggesting that the receptor molecule of the Ts cell is unique. However, none of the murine Ts cells that have been investigated for rearrangement were class II or class I major histocompatibility complex (MHC) restricted, as were the Th and Tc lines, respectively.In the present report we describe the establishment and functional characterization of Ts hybridomas that are antigen specific and I-A restricted. In this respect the Ts hybridomas are similar to Th cells.

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Section: T Cell Receptor Ct3 Gene Is Not Rearranged In Tsmentioning

confidence: 92%

Section: T Cell Receptor Ct3 Gene Is Not Rearranged In Tsmentioning

confidence: 99%

Section: Cytotoxic Assay and Cell Linesmentioning

confidence: 99%

See 1 more Smart Citation

Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes.

Blanckmeister¹,

Yamamoto²,

Davis³

et al. 1985

The Journal of Experimental Medicine

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“…A small (0.5-1 cm long) incision was made in the skin and subcutaneous tissue covering the spleen area, and then a very small cut (<0.5 cm) was made through the peritoneum near the spleen. With forceps introduced through the incision, the spleen was (20) and the 83-actin probe (1.1-kb Pst I-Pst I fragment). The probes were isolated inserts labeled with 32p by using a random-primer DNA-labeling kit (Boehringer Mannheim).…”

Section: Methodsmentioning

confidence: 99%

Heterogeneity of thymic epithelial cells in promoting T-lymphocyte differentiation in vivo.

Gutierrez

Palacios

1991

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

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To study in vivo the contribution of different thymic epithelial cells to T-lymphocyte differentiation, we have established several nontransformed thymic epithelial cell lines and developed an in vivo assay, not involving exposure to drugs or radiation, that permitted us to study the capacity of these epithelial lines to support T-cell differentiation. We found that cell lines EA2 and ET, which express markers of cortical epithelial cells, produce interleukin 7 mRNA and after being

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“…TCR ␣ and ␤ chain gene assembly is precisely regulated within the context of normal thymocyte development. TCR␤ chain genes are assembled in CD4 Ϫ ͞CD8 Ϫ [double negative (DN)] thymocytes (2)(3)(4). Expression of a TCR␤ chain, as a pre-TCR, results in signals that promote cellular expansion and developmental stage progression to the CD4 ϩ ͞CD8 ϩ [double positive (DP)] stage of thymocyte development (5).…”

Section: V(d)j Recombination ͉ Gene Rearrangement ͉ T Cell Repertoirementioning

confidence: 99%

Revision of T cell receptor α chain genes is required for normal T lymphocyte development

Huang

Sleckman

Kanagawa

2005

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

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To become mature ␣␤ T cells, developing thymocytes must first assemble a T cell receptor (TCR) ␤ chain gene encoding a TCR␤ chain that forms a pre-TCR. These cells then need to generate a TCR␣ chain gene encoding a TCR␣ chain, which, when paired with the TCR␤ chain, forms a selectable ␣␤ TCR. Newly generated VJ␣ rearrangements that do not encode TCR␣ chains capable of forming selectable ␣␤ TCRs can be excised from the chromosome and replaced with new VJ␣ rearrangements. Such replacement occurs through the process of TCR␣ chain gene revision whereby a V␣ gene segment upstream of the VJ␣ rearrangement is appended to a downstream J␣ gene segment. A multistep, gene-targeting approach was used to generate a modified TCR␣ locus (TCR␣ sJ ) with a limited capacity to undergo revision of TCR␣ chain genes. Thymocytes from mice homozygous for the TCR␣ sJ allele are defective in their ability to generate an ␣␤ TCR. Furthermore, those thymocytes that do generate an ␣␤ TCR have a diminished capacity to be positively selected, and TCR␣ sJ/sJ mice have significantly reduced numbers of mature ␣␤ T cells. Together, these findings demonstrate that normal T cell development relies on the ability of developing thymocytes to revise their TCR␣ chain genes.T he checkpoints imposed on developing T cells mandate that they generate T cell receptor (TCR) ␣ and ␤ chains that form an ␣␤ TCR capable of positive selection (1). TCR ␣ and ␤ chain gene assembly is precisely regulated within the context of normal thymocyte development. TCR␤ chain genes are assembled in CD4 Ϫ ͞CD8 Ϫ [double negative (DN)] thymocytes (2-4). Expression of a TCR␤ chain, as a pre-TCR, results in signals that promote cellular expansion and developmental stage progression to the CD4 ϩ ͞CD8 ϩ [double positive (DP)] stage of thymocyte development (5). Pre-TCR signals also promote TCR␣ chain gene assembly and prohibit further TCR␤ chain gene assembly through the process of allelic exclusion (5-7). Because allelic exclusion prohibits DP thymocytes from generating new TCR␤ chains, these cells must generate TCR␣ chains that form an ␣␤ TCR capable of positive selection if they are to become mature T cells.The genes encoding the TCR␣ chain are intermingled with TCR␦ chain genes in the TCR␣͞␦ locus ( Fig. 1) (8). TCR␣ variable region genes are assembled from V␣ and J␣ gene segments. There are Ϸ100 V␣ gene segments clustered in the 5Ј region of the mouse TCR␣͞␦ locus and 61 J␣ gene segments, spanning Ϸ60 kb, clustered in the 3Ј region of the locus (Fig. 1) (8). The V␣ and J␣ gene segments are oriented such that any rearrangement occurs by deletion, excising the intervening DNA from the chromosome (8).Thymocytes entering the DP compartment from the DN compartment express low TCR␤ chain levels, as the pre-TCR, and are referred to as TCR␤ low DP thymocytes. Initial V␣ rearrangements in these cells are targeted to the most 5Ј J␣ gene segments through the activity of the T early ␣ (TEA) promoter (9). A nonproductive VJ␣ rearrangement could be followed by a VJ␣ rearrangement on the oth...

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Ontogeny of the T-cell antigen receptor within the thymus

Cited by 236 publications

References 39 publications

Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes.

Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes.

Heterogeneity of thymic epithelial cells in promoting T-lymphocyte differentiation in vivo.

Revision of T cell receptor α chain genes is required for normal T lymphocyte development

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