Whiteley P J, Jensen P E, Pierce C W, Abruzzini A F, Kapp J A
Department of Pathology, Jewish Hospital of St. Louis, MO.
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2723-7. doi: 10.1073/pnas.85.8.2723.
Murine antibody responses to various species of insulin are under major histocompatibility complex-linked Ir gene control. Beef insulin differs from pork insulin by only two amino acids in the A-chain loop, yet strain C57BL/10 (B10) mice produce insulin-specific antibodies after immunization with beef insulin and fail to produce antibody after stimulation with pork insulin. Nevertheless, pork insulin primes helper T cells in B10 mice that can be demonstrated if insulin-specific Lyt-1-, -2+ suppressor T cells are removed. Not only do the pork insulin-primed helper and suppressor T cells cross-react with autologous insulin, but also rat insulin (the amino acid sequence of which is identical to mouse insulin) elicits functionally identical helper and suppressor T cells. In this report, we demonstrate that in B10 mice the frequency of helper T cells stimulated by pork insulin is equivalent to that stimulated by beef insulin and that helper T-cell clones induced by beef and pork insulin are major histocompatibility complex-restricted T cells that proliferate, produce lymphokines, and provide helper activity after activation. These helper T-cell clones exhibit different antigenic fine specificities: beef insulin-induced clones respond to beef insulin but not pork or autologous insulin, whereas pork insulin-induced clones cross-react with all species of insulin tested, including rat insulin. In addition, the helper activity of cloned pork insulin-specific T cells is abrogated by pork insulin-primed suppressor T cells. These data support the hypotheses that Ir gene control of antibody responses to certain antigens involves mechanisms used for maintenance of self-tolerance.
小鼠对各种胰岛素的抗体反应受主要组织相容性复合体连锁免疫反应基因（Ir基因）控制。牛胰岛素与猪胰岛素在A链环中仅有两个氨基酸不同，但C57BL/10（B10）品系小鼠在用牛胰岛素免疫后产生胰岛素特异性抗体，而在用猪胰岛素刺激后则不产生抗体。然而，如果去除胰岛素特异性Lyt-1-、-2+抑制性T细胞，猪胰岛素可在B10小鼠中激活辅助性T细胞。不仅猪胰岛素激活的辅助性和抑制性T细胞能与自身胰岛素发生交叉反应，而且大鼠胰岛素（其氨基酸序列与小鼠胰岛素相同）也能激活功能相同的辅助性和抑制性T细胞。在本报告中，我们证明在B10小鼠中，猪胰岛素刺激的辅助性T细胞频率与牛胰岛素刺激的频率相当，并且由牛胰岛素和猪胰岛素诱导的辅助性T细胞克隆是主要组织相容性复合体限制的T细胞，它们在激活后增殖、产生淋巴因子并提供辅助活性。这些辅助性T细胞克隆表现出不同的抗原精细特异性：牛胰岛素诱导的克隆对牛胰岛素有反应，但对猪胰岛素或自身胰岛素无反应，而猪胰岛素诱导的克隆与所有测试的胰岛素种类（包括大鼠胰岛素）都有交叉反应。此外，猪胰岛素特异性T细胞克隆的辅助活性被猪胰岛素激活的抑制性T细胞所消除。这些数据支持以下假说：Ir基因对某些抗原抗体反应的控制涉及维持自身耐受性的机制。
