Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: Forbidden clones revisited

Y. Naparstek, K. Baur, M. D. Reis, L. Breitman, T. W. Mak, R. S. Schwartz, M. P. Madaio

Research output: Contribution to journalArticle

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Abstract

MRL-lpr/lpr mice spontaneously develop a lethal form of systemic lupus erythematosus associated with massive lymphodenopathy, polyclonal B-cell activity, autoantibody production and antibody-dependent tissue injury. The sequence of events leading to B-cell proliferation and pathogenic autoantibody production are not clearly defined - abnormalities of both B and T cells have been observed. Isolation of individual T-cell clones would facilitate analysis of the cellular events involving both B and T cells that lead to autoantibody production. For this purpose, an autoreactive T-cell line (ARTC-1) was derived from the splenocytes of an unimmunized MRL-lpr/lpr mouse and maintained in culture by stimulation with syngeneic antigen presenting cells, without exogenous antigens. By T-cell receptor analysis it was demonstrated that ARC-1 cells developed as a clone even though no attempt was made to clone them in vitro: Southern blot analysis of ARTC-1 revealed a single rearrangement of the TcR β chain locus with the other TcR β chain gene remaining in the germline configuration. Northern blot analysis confirmed these findings and demonstrated that ARTC-1 utilized C(β)1 J(β) 1.3 exclusively. ARTC-1 had atypical MHC requirements for activation: antigen-presenting cells bearing both I-A(k) and I-E(k) major histocompatibility complex class II antigens were required for maximal proliferation of the ARTC-1 clone. Activated ARTC-l secreted solbule factors that induced B-cell proliferation, immunoglobulin secretion, and anti-DNA antibody production. Unregulated cells of the AR-TC1 type could, therefore, lead to polyclonal B-cell activation and autoantibody production in vivo in the absence of exogeneous antigenic stimulation.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalJournal of Molecular and Cellular Immunology
Volume4
Issue number1
StatePublished - Jan 1 1988

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B-Lymphocytes
Clone Cells
T-Lymphocytes
Autoantibodies
Antigen-Presenting Cells
Antibody Formation
Cell Proliferation
AIDS-Related Complex
T-Cell Receptor Genes
Antinuclear Antibodies
Histocompatibility Antigens Class II
Cytotoxic T-Lymphocytes
T-Cell Antigen Receptor
Southern Blotting
Major Histocompatibility Complex
Northern Blotting
Systemic Lupus Erythematosus
Immunoglobulins
Antigens
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Naparstek, Y., Baur, K., Reis, M. D., Breitman, L., Mak, T. W., Schwartz, R. S., & Madaio, M. P. (1988). Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: Forbidden clones revisited. Journal of Molecular and Cellular Immunology, 4(1), 35-43.

Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice : Forbidden clones revisited. / Naparstek, Y.; Baur, K.; Reis, M. D.; Breitman, L.; Mak, T. W.; Schwartz, R. S.; Madaio, M. P.

In: Journal of Molecular and Cellular Immunology, Vol. 4, No. 1, 01.01.1988, p. 35-43.

Research output: Contribution to journalArticle

Naparstek, Y, Baur, K, Reis, MD, Breitman, L, Mak, TW, Schwartz, RS & Madaio, MP 1988, 'Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: Forbidden clones revisited', Journal of Molecular and Cellular Immunology, vol. 4, no. 1, pp. 35-43.
Naparstek, Y. ; Baur, K. ; Reis, M. D. ; Breitman, L. ; Mak, T. W. ; Schwartz, R. S. ; Madaio, M. P. / Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice : Forbidden clones revisited. In: Journal of Molecular and Cellular Immunology. 1988 ; Vol. 4, No. 1. pp. 35-43.
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