Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

Andy L. Johnson; L. Aravind; Natalia Shulzhenko; Andre Morgun; See Young Choi; Tanya L. Crockford; Teresa Lambe; Heather Domaschenz; Edyta M. Kucharska; Lixin Zheng; Carola G. Vinuesa; Michael J. Lenardo; Christopher C. Goodnow; Richard J. Cornall; Ronald H. Schwartz

doi:10.1038/ni.1769

Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

Andy L. Johnson, L. Aravind, Natalia Shulzhenko, Andre Morgun, See Young Choi, Tanya L. Crockford, Teresa Lambe, Heather Domaschenz, Edyta M. Kucharska, Lixin Zheng, Carola G. Vinuesa, Michael J. Lenardo, Christopher C. Goodnow, Richard J. Cornall^*, Ronald H. Schwartz

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

100 Citations (Scopus)

Abstract

T cell antigen receptor (TCR) signaling in CD4⁺CD8⁺ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.

Original language	English
Pages (from-to)	831-839
Number of pages	9
Journal	Nature Immunology
Volume	10
Issue number	8
DOIs	https://doi.org/10.1038/ni.1769
Publication status	Published - 2009

Access to Document

10.1038/ni.1769

Cite this

Johnson, A. L., Aravind, L., Shulzhenko, N., Morgun, A., Choi, S. Y., Crockford, T. L., Lambe, T., Domaschenz, H., Kucharska, E. M., Zheng, L., Vinuesa, C. G., Lenardo, M. J., Goodnow, C. C., Cornall, R. J., & Schwartz, R. H. (2009). Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nature Immunology, 10(8), 831-839. https://doi.org/10.1038/ni.1769

@article{b30d5518126c4d99be2d339039b613ce,

title = "Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection",

abstract = "T cell antigen receptor (TCR) signaling in CD4+CD8+ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.",

author = "Johnson, {Andy L.} and L. Aravind and Natalia Shulzhenko and Andre Morgun and Choi, {See Young} and Crockford, {Tanya L.} and Teresa Lambe and Heather Domaschenz and Kucharska, {Edyta M.} and Lixin Zheng and Vinuesa, {Carola G.} and Lenardo, {Michael J.} and Goodnow, {Christopher C.} and Cornall, {Richard J.} and Schwartz, {Ronald H.}",

year = "2009",

doi = "10.1038/ni.1769",

language = "English",

volume = "10",

pages = "831--839",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "8",

}

Johnson, AL, Aravind, L, Shulzhenko, N, Morgun, A, Choi, SY, Crockford, TL, Lambe, T, Domaschenz, H, Kucharska, EM, Zheng, L, Vinuesa, CG, Lenardo, MJ, Goodnow, CC, Cornall, RJ & Schwartz, RH 2009, 'Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection', Nature Immunology, vol. 10, no. 8, pp. 831-839. https://doi.org/10.1038/ni.1769

TY - JOUR

T1 - Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

AU - Johnson, Andy L.

AU - Aravind, L.

AU - Shulzhenko, Natalia

AU - Morgun, Andre

AU - Choi, See Young

AU - Crockford, Tanya L.

AU - Lambe, Teresa

AU - Domaschenz, Heather

AU - Kucharska, Edyta M.

AU - Zheng, Lixin

AU - Vinuesa, Carola G.

AU - Lenardo, Michael J.

AU - Goodnow, Christopher C.

AU - Cornall, Richard J.

AU - Schwartz, Ronald H.

PY - 2009

Y1 - 2009

N2 - T cell antigen receptor (TCR) signaling in CD4+CD8+ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.

AB - T cell antigen receptor (TCR) signaling in CD4+CD8+ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.

UR - http://www.scopus.com/inward/record.url?scp=67651149464&partnerID=8YFLogxK

U2 - 10.1038/ni.1769

DO - 10.1038/ni.1769

M3 - Article

SN - 1529-2908

VL - 10

SP - 831

EP - 839

JO - Nature Immunology

JF - Nature Immunology

IS - 8

ER -

Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

Abstract

Access to Document

Other files and links

Fingerprint

Cite this