Viral degradation of the MHC class I peptide loading complex

被引:91
作者
Boname, JM
de Lima, BD
Lehner, PJ
Stevenson, PG
机构
[1] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England
[2] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/S1074-7613(04)00047-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:305 / 317
页数:13
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