A peptide derived from an autoantibody can stimulate t cells in the (nzb × nzw)f<sub>1</sub> mouse model of systemic lupus erythematosus

Ebling, Fanny M.; Tsao, Betty P.; Singh, Ram Raj; Sercarz, Eli E.; Hahn, Bevra H.

doi:10.1002/art.1780360311

Cited by 69 publications

(57 citation statements)

References 33 publications

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“…Thus, immunization of NZB͞W mice with the latter CDR2 peptide, as well as with a cryptic peptide of the same antibody, increased plasma levels of anti-DNA IgG antibodies, accelerating immune complex deposition in the kidneys and nephritis (22,23). The differences between the latter results and those of tolerance experiments reported here might be due to differences either in the peptides used or between the experimental model of induced SLE used by us and the spontaneous model of SLE studied by Hahn and coworkers (22,23).…”

Section: Discussionmentioning

confidence: 99%

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Waisman

Ruiz

Israeli

et al. 1997

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

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Experimental systemic lupus erythematosus (SLE) can be induced in naive mice by immunization with a murine monoclonal anti-DNA antibody (mAb), 5G12, that bears a major idiotype designated 16͞6 Id. Strain-dependent differences were observed in the proliferative responses of lymph node cells of mice immunized with two peptides based on the sequences of the complementarity determining region (CDR) 1 and 3 of mAb 5G12. The capacity of the peptides to bind to major histocompatibility complex class II molecules correlated with the proliferative responses. Immunization of high responder strains with the CDR-based peptides led to production of autoantibodies and clinical manifestations characteristic to experimental SLE. The CDR-based peptides could prevent autoantibody production in neonatal mice that were immunized later either with the peptide or with the pathogenic autoantibody. Furthermore, the peptides inhibited specific proliferation of lymph node cells of mice immunized with the same peptide, with mAb 5G12 or with the human mAb anti-DNA, 16͞6 Id. Thus, the CDR-based peptides are potential candidates for therapy of SLE.

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Section: Discussionmentioning

confidence: 99%

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Waisman

Ruiz

Israeli

et al. 1997

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

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“…Several groups have reported evidence in support of receptor presentation in autoimmunity (27,30,31,(35)(36)(37)(38)(39)(40). In a preceding study, we conducted a genealogical analysis of somatic mutations within an autoreactive B cell lineage obtained from a spontaneously diseased SNF 1 mouse.…”

Section: T Cell Tolerance To Germline-encoded Antibody Sequences In Amentioning

confidence: 99%

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Guo

Smith

Guth

et al. 2005

The Journal of Immunology

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The BCR V region has been implicated as a potential avenue of T cell help for autoreactive B cells in systemic lupus erythematosus. In principle, either germline-encoded or somatically generated sequences could function as targets of such help. Preceding studies have indicated that class II MHC-restricted T cells in normal mice attain a state tolerance to germline-encoded Ab diversity. In this study, we tested whether this tolerance is intact in systemic lupus erythematosus-prone (New Zealand Black × SWR)F1 mice (SNF1). Using a hybridoma sampling approach, we found that SNF1 T cells were tolerant to germline-encoded Ab sequences. Specifically, they were tolerant to germline-encoded sequences derived from a lupus anti-chromatin Ab that arose spontaneously in this strain. This was true both for diseased and prediseased mice. Thus, there does not appear to be a global defect in T cell tolerance to Ab V regions in this autoimmune-prone strain either before or during autoimmune disease.

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“…15-mer overlapping peptides representing the entire V H D region sequence of an anti-dsDNA mAb, A6.1, were synthesized using a modified pin synthesis or a macrocrown method (14). Each 15-mer peptide overlapped its neighbor by 10 residues.…”

Section: Peptidesmentioning

confidence: 99%

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

Singh

Ebling

Albuquerque

et al. 2002

The Journal of Immunology

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Many individuals develop a single or a few brief episodes of autoimmunity from which they recover. Mechanisms that quell pathologic autoimmunity following such a breakdown of self-tolerance are not clearly understood. In this study, we show that in nonautoimmune mice, dsDNA-specific autoreactive B cells exist but remain inactive. This state of inactivation in dsDNA-specific B cells could be disrupted by autoreactive Th cells; in this case T cells that react with peptides from the VH region of anti-DNA Abs (hereafter called anti-VH T cells). Immunization with anti-DNA mAb, its γ-chain or peptides derived from its VH region induced anti-VH Th cells, IgG anti-dsDNA Ab, and proteinuria. The breakdown of B cell tolerance in nonautoimmune mice, however, was short-lived: anti-DNA Ab and nephritis subsided despite subsequent immunizations. The recovery from autoimmunity temporally correlated with the appearance of T cells that inhibited anti-DNA Ab production. Such inhibitory T cells secreted TGFβ; the inhibition of anti-DNA Ab production by these cells was partly abolished by anti-TGFβ Ab. Even without immunization, nonautoimmune mice possess T cells that can inhibit autoantibody production. Thus, inhibitory T cells in nonautoimmune mice may normally inhibit T-dependent activation of autoreactive B cells and/or reverse such activation following stimulation by Th cells. The induction of such inhibitory T cells may play a role in protecting nonautoimmune mice from developing chronic autoimmunity.

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A peptide derived from an autoantibody can stimulate t cells in the (nzb × nzw)f₁ mouse model of systemic lupus erythematosus

Cited by 69 publications

References 33 publications

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

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A peptide derived from an autoantibody can stimulate t cells in the (nzb × nzw)f1 mouse model of systemic lupus erythematosus

Cited by 69 publications

References 33 publications

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

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A peptide derived from an autoantibody can stimulate t cells in the (nzb × nzw)f₁ mouse model of systemic lupus erythematosus