The murine T-cell receptor uses a limited repertoire of expressed Vβ gene segments

Barth, Richard K.; Kim, Byung S.; Lan, Nancy C.; Hunkapiller, Tim; Sobieck, Nancy; Winoto, Astar; Gershenfeld, Howard K.; Okada, Craig; Hansburg, Daniel; Weissman, Irving L.; Hood, Leroy

doi:10.1038/316517a0

Cited by 280 publications

(147 citation statements)

References 53 publications

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“…Our approaches to immunology and biology were quite complementary, and I later took a sabbatical with Lee in 1981 to learn how to work with genes myself. He had some great students and fellows at the time, e.g., Mark Davis, Mike Hunkapiller, Michael Steinmetz, Phil Early, and Stuart Kim, and we began a series of collaborations where my lab would isolate pure normal cell subsets and together we would examine the germline or rearranged status of immunoglobulin genes (73,74) and then TCR genes (75). We continue to collaborate to this day.…”

Section: The Thymus Thymic Maturation B Lymphocyte Development Hommentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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Section: The Thymus Thymic Maturation B Lymphocyte Development Hommentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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“…Under the following assumptions-1, all rearrangements present in the sample have an equal probability of being sequenced; 2, sequence obtention can be considered as a random draw with replacement, i.e., the obtention of a given sequence does not alter the probabilities to observe the following sequences; 3, the frequencies of all rearrangements are identical, i.e., all rearrangements correspond to the similar number of transcripts within the sample-the equation used by Barth et al (20) and Behlke et al (21) was used to estimate the maximum probable number of distinct CDR3 sequences found in the cDNA preparation. Namely, the maximum likelihood estimate (MLE) of the number of distinct sequences is the value that maximizes the equation:…”

Section: Statistical Calculationsmentioning

confidence: 99%

Size Estimate of the αβ TCR Repertoire of Naive Mouse Splenocytes

Casrouge

Beaudoing

Dalle

et al. 2000

The Journal of Immunology

285

236

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The diversity of the T cell repertoire of mature T splenocytes is generated, in the thymus, by pairing of α and β variable domains of the αβ TCR and by the rearrangements of various gene segments encoding these domains. In the periphery, it results from competition between various T cell subpopulations including recent thymic migrants and long-lived T cells. Quantitative data on the actual size of the T cell repertoire are lacking. Using PCR methods and extensive sequencing, we have measured for the first time the size of the TCR-αβ repertoire of naive mouse T splenocytes. There are 5–8 × 105 different nucleotide sequences of BV chains in the whole spleen of young adult mice. We have also determined the size of the BV repertoire in a subpopulation of AV2+ T splenocytes, which allows us to provide a minimum estimate of the αβ repertoire. We find that the mouse spleen harbors about 2 × 106 clones of about 10 cells each. This figure, although orders of magnitude smaller than the maximum theoretical diversity (estimated up to 1015), is still large enough to maintain a high functional diversity.

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“…Somatic diversification includes junctional diversity, the flexible joining of gene segments at different sites (10, 11), and N-region diversification, the addition of random nucleotides at rearranged gene segment junctions (10,12 (17), perhaps in keeping with the dual requirement of the T-cell receptor to recognize antigen in the context of a MHC molecule. In any case, much of the diversity in the j3 chain seems to be focused at the carboxyl end of the V region through the heavy use ofjunctional and N-region diversity, the unique ability to use Do segments in all three translational reading frames, and the use of a large family of JP segments that are, on average, considerably more diverse than JH or JK segments (15)(16)(17).We have analyzed the expression of 13-chain genes in human peripheral lymphocytes in order to ascertain whether the strategies for diversification observed in mouse ( chains are a standard feature ofthe T-cell immune response in higher vertebrates. We conclude that (i) the strategy of maintaining a limited repertoire of highly heterogeneous Va gene segments is shared between mice and humans; (it) …”

mentioning

confidence: 99%

Diversity and structure of human T-cell receptor beta-chain variable region genes.

Concannon¹,

Pickering²,

Kung³

et al. 1986

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

139

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The nucleotide sequences of 27 T-cell receptor P cDNA clones isolated from a human peripheral lymphocyte library were determined and compared to five additional published sequences. These cDNA clones represent 22 distinct Mouse 13-chain genes have at their disposal all of the diversification mechanisms that are used by immunoglobulin genes but one. These include germ-line diversity, the maintenance of a multiplicity of V, D, and J gene segments, combinational diversity, the joining of available gene segments in all possible combinations, and somatic diversification (8,9). Somatic diversification includes junctional diversity, the flexible joining of gene segments at different sites (10, 11), and N-region diversification, the addition of random nucleotides at rearranged gene segment junctions (10,12 (17), perhaps in keeping with the dual requirement of the T-cell receptor to recognize antigen in the context of a MHC molecule. In any case, much of the diversity in the j3 chain seems to be focused at the carboxyl end of the V region through the heavy use ofjunctional and N-region diversity, the unique ability to use Do segments in all three translational reading frames, and the use of a large family of JP segments that are, on average, considerably more diverse than JH or JK segments (15)(16)(17).We have analyzed the expression of 13-chain genes in human peripheral lymphocytes in order to ascertain whether the strategies for diversification observed in mouse ( chains are a standard feature ofthe T-cell immune response in higher vertebrates. We conclude that (i) the strategy of maintaining a limited repertoire of highly heterogeneous Va gene segments is shared between mice and humans; (it) 6598The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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The murine T-cell receptor uses a limited repertoire of expressed Vβ gene segments

Cited by 280 publications

References 53 publications

How One Thing Led to Another

How One Thing Led to Another

Size Estimate of the αβ TCR Repertoire of Naive Mouse Splenocytes

Diversity and structure of human T-cell receptor beta-chain variable region genes.

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