A peptide based on the CDR3 of an anti-DNA antibody of experimental SLE origin is also a dominant T-cell epitope in (NZBXNZW)F1 lupus-prone mice

Brosh, Naama; Dayan, Molly; Fridkin, Mati; Mozes, Edna

doi:10.1016/s0165-2478(00)00161-9

Cited by 15 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, B cells process and present their endogenous BCR as short Id peptides on MHC class II to T cells that may recognize V-region Id peptides (27)(28)(29)(30). It was shown that V regions derived from anti-dsDNA B cells of normal mice (50), as well as BWF1 mice (17,18), contain Id CD4 + T cell epitopes. Further, Id-specific CD4 + T cells have been found in humans suffering from SLE (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

Aas-Hanssen

Funderud

Thompson

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is marked by a Th cell–dependent B cell hyperresponsiveness, with frequent germinal center reactions and hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H chain (IgVH). B cells can present V region–derived Id peptides on their MHC class II molecules to Id-specific Th cells. We show that Id-specific Th cells support the proliferation of anti-dsDNA Id+ B cells in mice suffering from systemic autoimmune disease with SLE-like features. Mice developed marked clonal expansions of B cells; half of the IgVH sequences were clonally related. Anti-dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell–B cell collaboration supported the production of classical anti-dsDNA Abs, recapitulating the characteristics of such Abs in SLE. The results support the concept that Id-specific Th cells may trigger the development of SLE and suggest that manipulation of the Id-specific T cell repertoire could play a role in treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

Aas-Hanssen

Funderud

Thompson

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…a Mab 16/6 CDR-1 based peptide, TGYYMQWV KQSPEKSLEWIG, prevented autoantibody production when these mice were later immunized with peptide or native 16/6 antibody [68] to induce disease; moreover, immunization of the CDR-1-based peptide, as well as the CDR3-based peptide, YYCARFLWEPYAMDYWGQGS, into young mice accelerated disease [70]. In addition, injection of peptide-reactive T-cell lines into nonautoimmune SJL mice induced increased autoantibody production and elevated proteinurea [71].…”

Section: Molecular Analysis Of Id Lnmentioning

confidence: 99%

Molecular Identification of Pathogenetic IdLNF+1 Autoantibody Idiotypes Derived from the (NZB×SWR)F1 Model for Systemic Lupus Erythematosus

Price

Knupp

Tatum

et al. 2002

Journal of Autoimmunity

View full text Add to dashboard Cite

A peptide based on the CDR3 of an anti-DNA antibody of experimental SLE origin is also a dominant T-cell epitope in (NZBXNZW)F1 lupus-prone mice

Cited by 15 publications

References 18 publications

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

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

Molecular Identification of Pathogenetic IdLNF+1 Autoantibody Idiotypes Derived from the (NZB×SWR)F1 Model for Systemic Lupus Erythematosus

Contact Info

Product

Resources

About