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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.

Original publication

DOI

10.1084/jem.20020797

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

12/2002

Volume

196

Pages

1403 - 1414

Addresses

Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden.

Keywords

Killer Cells, Natural, K562 Cells, Humans, Protein Sorting Signals, Chaperonin 60, Lectins, C-Type, Receptors, Immunologic, Antigens, CD, Histocompatibility Antigens Class I, HLA Antigens, Lymphocyte Activation, Cytotoxicity, Immunologic, Antigen Presentation, Amino Acid Sequence, Molecular Sequence Data, Receptors, KIR, NK Cell Lectin-Like Receptor Subfamily D, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily C