Defective TCR expression in transgenic mice constructed using cDNA‐based α‐ and β‐chain genes under the control of heterologous regulatory elements

Immunology and Cell Biology - Tập 76 Số 1 - Trang 34-40 - 1998
Megan Barnden1,2, Jan Allison3, William R. Heath3, Federico Carbone1
1Department of Pathology and Immunology, Monash Medical School, Commercial Road, Prahran, Victoria, Australia
2Present address: Department of Microbiology and Immunology, The University of Melbourne, Royal Parade, Parkville, Vic. 3052, Australia.
3The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Tóm tắt

We describe the generation of ovalbumin (OVA)‐specific, MHC class II‐restricted αβ T cell receptor (TCR) transgenic mice. Initial attempts at generating these transgenic mice utilized heterologous regulatory elements to drive the expression of cDNA genes encoding the separate α‐ and β‐chains of the TCR. Unexpectedly, T cells bearing the transgenic αβ TCR failed to emerge from the thymus in these mice, although the transgenes did modify endogenous TCR expression. However, subsequent modification of the approach which enabled expression of the TCR β‐chain under the control of its natural regulatory elements generated mice whose peripheral T cells expressed the transgenic TCR and were capable of antigen‐dependent proliferation. These results show that successful generation of MHC class II‐restricted, OVA‐specific αβTCR transgenic mice was dependent upon combining cDNA‐ and genomic DNA‐based constructs for expression of the respective α‐ and β‐chains of the TCR.

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Tài liệu tham khảo

10.1038/333742a0

10.1038/335730a0

10.1038/336073a0

10.1038/340559a0

Berg LJ, 1989, Antigen/MHC‐specific T cells are preferentially exported from the thymus in the presence of their MHC ligand., Nature, 359, 330

Scott B, 1989, The generation of mature T cells requires interaction of the αβ T cell receptor with major histocompatibility antigens., Nature, 338, 593, 10.1038/338591a0

10.1016/0022-1759(95)00002-R

10.1038/342559a0

10.1155/1993/98015

Turner SJ, 1996, TCR α‐chain usage can determine antigen‐selected TCR β‐chain repertoire diversity., J. Immunol., 157, 4979, 10.4049/jimmunol.157.11.4979

Kaye J, 1992, Involvement of the same region of the T cell antigen receptor in thymic selection and foreign peptide recognition., J. Immunol., 148, 3342, 10.4049/jimmunol.148.11.3342

Carbone FR, 1992, T cell receptor α‐chain pairing determines the specificity of residue 262 within the Kb‐restricted, ovalbumin257–264 determinant., Int. Immunol., 8, 861, 10.1093/intimm/4.8.861

10.1002/j.1460-2075.1988.tb02871.x

10.1084/jem.179.5.1539

10.1073/pnas.88.18.8077

Bill J, 1990, Class I and class II MHC gene products differentially affect the fate of Vβ5 bearing thymocytes., J. Mol. Cell Immunol., 4, 269

10.1016/0092-8674(94)90169-4

Pircher H, 1989, T cell tolerance to Mlsa encoded antigens in T cell receptor Vβ8.1 chain transgenic mice., EMBO J., 8, 719, 10.1002/j.1460-2075.1989.tb03431.x

10.1084/jem.183.5.2087

Aspinall R, 1997, Age‐associated thymic atrophy in the mouse due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development., J. Immunol., 158, 3037, 10.4049/jimmunol.158.7.3037

10.1038/360225a0

10.1126/science.1968289

10.1084/jem.176.6.1733

10.1126/science.8303275

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Immunology and Cell Biology

Tập 76 Số 1

34-40

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