Ebling F M, Tsao B P, Singh R R, Sercarz E, Hahn B H
Department of Medicine, University of California, Los Angeles 90024.
Arthritis Rheum. 1993 Mar;36(3):355-64. doi: 10.1002/art.1780360311.
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.
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.
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.
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.
评估源自抗DNA的肽刺激同基因T淋巴细胞以及影响（新西兰黑鼠×新西兰白鼠）F1（NZB/W）小鼠狼疮的能力。
我们（通过盖森针技术）合成了重叠的12肽，这些肽概括了来自一只NZB/W小鼠的致肾炎单克隆IgG2a抗DNA抗体（A6.1）VH区的氨基酸序列。脾T细胞与这些肽一起培养；多个实验检测了包含三碱基基序（KFKGK）的12肽和16肽。我们用12肽免疫20周龄的NZB/W小鼠，并评估它们是否有肾炎迹象以及血浆和肾小球中抗体的量。
三组肽导致未免疫的年轻小鼠脾细胞增殖。12肽FYNQKFKGKATL和16肽GDTFYNQKFKGKATLT均刺激纯化的T细胞。KXKXK基序在15%的小鼠Ig VH中出现（NBRF蛋白质数据库），而在NZB/W抗DNA单克隆抗体中出现率为100%（6/6）。用12肽免疫会增加血浆中IgG、抗DNA和免疫复合物的水平以及肾小球中抗DNA的水平；肾炎加速发展。
NZB/W抗DNA在其VH区含有刺激自身T细胞的肽序列。至少一种基序在NZB/W抗DNA中很常见。如果一些活化的T细胞提供帮助，这种机制可能有助于小鼠狼疮中自身抗体的持续上调。
