Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice

Paul Zhou, Gary D. Anderson, Suresh Savarirayan, Hidetoshi Inoko, Chella S. David

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA X B10.M)F2 or (SWR X SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQβ-specific mAb demonstrated that DQβ molecules in association with mouse Aαf molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells, but not Vβ8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQβ+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, Aαf/DQβ hybrid molecules may possess the same self-peptide- (or superantigen)-presenting epitope as Eα/Eβ molecules critical for deletion of Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mouse CD4 and mouse Aa chain is required for the clonal deletion.

Original languageEnglish (US)
Pages (from-to)854-859
Number of pages6
JournalJournal of Immunology
Volume146
Issue number3
StatePublished - Feb 1 1991

Fingerprint

HLA-DQ Antigens
Transgenic Mice
T-Lymphocytes
Thymocytes
Transgenes
Clonal Deletion
Superantigens
Cosmids
HLA-B Antigens
Thymus Gland
Genes
Epitopes
B-Lymphocytes
Spleen
Embryonic Structures
Clone Cells
Cell Line
Peptides
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Zhou, P., Anderson, G. D., Savarirayan, S., Inoko, H., & David, C. S. (1991). Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice. Journal of Immunology, 146(3), 854-859.

Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice. / Zhou, Paul; Anderson, Gary D.; Savarirayan, Suresh; Inoko, Hidetoshi; David, Chella S.

In: Journal of Immunology, Vol. 146, No. 3, 01.02.1991, p. 854-859.

Research output: Contribution to journalArticle

Zhou, P, Anderson, GD, Savarirayan, S, Inoko, H & David, CS 1991, 'Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice', Journal of Immunology, vol. 146, no. 3, pp. 854-859.
Zhou P, Anderson GD, Savarirayan S, Inoko H, David CS. Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice. Journal of Immunology. 1991 Feb 1;146(3):854-859.
Zhou, Paul ; Anderson, Gary D. ; Savarirayan, Suresh ; Inoko, Hidetoshi ; David, Chella S. / Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice. In: Journal of Immunology. 1991 ; Vol. 146, No. 3. pp. 854-859.
@article{856ec1c66bb242bcb8a0fc53dd0b6d39,
title = "Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice",
abstract = "DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA X B10.M)F2 or (SWR X SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQβ-specific mAb demonstrated that DQβ molecules in association with mouse Aαf molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells, but not Vβ8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQβ+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, Aαf/DQβ hybrid molecules may possess the same self-peptide- (or superantigen)-presenting epitope as Eα/Eβ molecules critical for deletion of Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mouse CD4 and mouse Aa chain is required for the clonal deletion.",
author = "Paul Zhou and Anderson, {Gary D.} and Suresh Savarirayan and Hidetoshi Inoko and David, {Chella S.}",
year = "1991",
month = "2",
day = "1",
language = "English (US)",
volume = "146",
pages = "854--859",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Thymic deletion of Vβ11+, Vβ5+ T cells in H-2E negative, HLA-DQβ+ single transgenic mice

AU - Zhou, Paul

AU - Anderson, Gary D.

AU - Savarirayan, Suresh

AU - Inoko, Hidetoshi

AU - David, Chella S.

PY - 1991/2/1

Y1 - 1991/2/1

N2 - DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA X B10.M)F2 or (SWR X SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQβ-specific mAb demonstrated that DQβ molecules in association with mouse Aαf molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells, but not Vβ8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQβ+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, Aαf/DQβ hybrid molecules may possess the same self-peptide- (or superantigen)-presenting epitope as Eα/Eβ molecules critical for deletion of Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mouse CD4 and mouse Aa chain is required for the clonal deletion.

AB - DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA X B10.M)F2 or (SWR X SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQβ-specific mAb demonstrated that DQβ molecules in association with mouse Aαf molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells, but not Vβ8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQβ+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, Aαf/DQβ hybrid molecules may possess the same self-peptide- (or superantigen)-presenting epitope as Eα/Eβ molecules critical for deletion of Vβ11-, Vβ5.1-, and Vβ5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mouse CD4 and mouse Aa chain is required for the clonal deletion.

UR - http://www.scopus.com/inward/record.url?scp=0026065897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026065897&partnerID=8YFLogxK

M3 - Article

C2 - 1899097

AN - SCOPUS:0026065897

VL - 146

SP - 854

EP - 859

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -