高迁移率族蛋白(high mobility group box,HMGB)是一种非组蛋白染色体蛋白质。在正常情况下位于细胞内，参与多种生物学过程，包括维持核小体结构、调节基因转录、核糖核酸形成、DNA修复、编码免疫球蛋白可变区的V、D、J基因片段重组、分化和发展等。
Nature最新一项研究表明，染色体HMGB 蛋白HMGB1、 HMGB2 和HMGB3是所有由核酸受体调控的先天免疫反应的激发所必不可少的。HMGB蛋白与所测试的所有产生免疫反应的核酸相结合（不管它们被认为是Toll样受体的配体还是细胞溶质配体），说明它们可能有一个生理作用，即充当细胞内核酸的普适性“哨兵”。
Nature 462, 99-103 (5 November 2009)
The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors1, 2. However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we show that high-mobility group box (HMGB) proteins 1, 2 and 3 function as universal sentinels for nucleic acids. HMGBs bind to all immunogenic nucleic acids examined with a correlation between affinity and immunogenic potential. Hmgb1 -/- and Hmgb2 -/- mouse cells are defective in type-I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate the cytosolic nucleic-acid-sensing receptors; cells in which the expression of all three HMGBs is suppressed show a more profound defect, accompanied by impaired activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-B. The absence of HMGBs also severely impairs the activation of TLR3, TLR7 and TLR9 by their cognate nucleic acids. Our results therefore indicate a hierarchy in the nucleic-acid-mediated activation of immune responses, wherein the selective activation of nucleic-acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders.