A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition

被引:207
作者
Michaëlsson, J
de Matos, CT
Achour, A
Lanier, LL
Kärre, K
Söderström, K
机构
[1] Karolinska Inst, MTC, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden
[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA
关键词
CD94/NKG2; MHC class I; cellular stress; peptide interference; hsp60;
D O I
10.1084/jem.20020797
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule which presents a restricted set of nonameric peptides, derived mainly from the signal sequence of other MHC class I molecules. It interacts with CD94/NKG2 receptors expressed on the surface of natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also presents a peptide derived from the leader sequence of human heat shock protein 60 (hsp60). This peptide gains access to HLA-E intracellularly, resulting in up-regulated HLA-E/hsp60 signal peptide cell-surface levels on stressed cells. Notably, HLA-E molecules in complex with the hsp60 signal peptide are no longer recognized by CD94/NKG2A inhibitory receptors. Thus, during cellular stress an increased proportion of HLA-E molecules may bind the nonprotective hsp60 signal peptide, leading to a reduced capacity to inhibit a major NK cell population. Such stress induced peptide interference would gradually uncouple CD94/NKG2A inhibitory recognition and provide a mechanism for NK cells to detect stressed cells in a peptide-dependent manner.
引用
收藏
页码:1403 / 1414
页数:12
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