A peptide derived from an autoantibody can stimulate T cells in the (NZB x NZW)F1 mouse model of systemic lupus erythematosus.

OBJECTIVE: To assess the ability of peptides derived from anti-DNA to stimulate syngeneic T lymphocytes and influence lupus in (NZB x NZW)F1 (NZB/W) mice.
METHODS: We synthesized (by Geysen pin method) overlapping 12-mer peptides recapitulating the amino acid sequence of the VH region of a nephritogenic monoclonal IgG2a anti-DNA antibody (A6.1) from an NZB/W mouse. Splenic T cells were cultured with the peptides; multiple experiments assayed 12-mer and 16-mer peptides which contained a triple-base motif (KFKGK). We immunized 20-week-old NZB/W mice with the 12-mer and evaluated them for evidence of nephritis and for quantities of antibodies in plasma and glomeruli.
RESULTS: Three clusters of peptides caused proliferation of spleen cells from young, nonimmunized mice. Both the 12-mer FYNQKFKGKATL and the 16-mer GDTFYNQKFKGKATLT peptides stimulated purified T cells. The KXKXK motif occurs in 15% of murine Ig VH (NBRF protein database), compared with 100% (6 of 6) of NZB/W anti-DNA monoclonal antibody. Immunization with the 12-mer peptide increased plasma levels of IgG, anti-DNA, and immune complexes, and levels of anti-DNA in glomeruli; nephritis was accelerated.
CONCLUSION: NZB/W anti-DNA contain peptide sequences in their VH regions that stimulate self-T cells. At least one motif is frequent in NZB/W anti-DNA. If some activated T cells provide help, this mechanism may contribute to sustained up-regulation of autoantibodies in murine lupus.