Boname Jessica M, de Lima Brigitte D, Lehner Paul J, Stevenson Philip G
Division of Virology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Immunity. 2004 Mar;20(3):305-17. doi: 10.1016/s1074-7613(04)00047-0.
The murine gamma-herpesvirus-68 MK3 protein inhibits CD8(+) T cell recognition by ubiquitinating the cytoplasmic tails of classical MHC class I heavy chains. Here we show that MK3 also provides the first example of a protein that degrades tapasin and TAP. The degradation was MK3 RING finger dependent and primarily affected TAP. MK3 associated with TAP1 in the absence of tapasin or TAP2, suggesting that TAP1 was a primary binding partner in the peptide loading complex. TAP2 also played a major role in MK3 stability and function. By degrading TAP, therefore, MK3 limited its own expression. However, TAP degradation also broadened the MK3 inhibitory repertoire and achieved a remarkable resistance to MHC class I upregulation by interferon-gamma, suggesting that it represents a specific adaptation to immune evasion in lymphoid tissue.
鼠γ-疱疹病毒68型的MK3蛋白通过泛素化经典MHC I类重链的胞质尾部来抑制CD8(+) T细胞识别。在此我们表明，MK3还是首个能降解塔帕辛（tapasin）和抗原加工相关转运体（TAP）的蛋白实例。这种降解依赖于MK3的环指结构域，且主要影响TAP。在没有塔帕辛或TAP2的情况下，MK3与TAP1结合，这表明TAP1是肽装载复合物中的主要结合伴侣。TAP2在MK3的稳定性和功能中也起主要作用。因此，通过降解TAP，MK3限制了其自身的表达。然而，TAP的降解也拓宽了MK3的抑制范围，并对γ干扰素介导的MHC I类上调产生了显著抗性，这表明它代表了在淋巴组织中对免疫逃逸的一种特殊适应。
