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Intracellular cysteine residues in the tail of MHC class I proteins are crucial for extracellular recognition by leukocyte Ig-like receptor 1.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Sep 15; Vol. 179 (6), pp. 3655-61. - Publication Year :
- 2007
-
Abstract
- The activity of NK cells is regulated by activating receptors that recognize mainly stress-induced ligands and by inhibitory receptors that recognize mostly MHC class I proteins on target cells. Comparing the cytoplasmic tail sequences of various MHC class I proteins revealed the presence of unique cysteine residues in some of the MHC class I molecules which are absent in others. To study the role of these unique cysteines, we performed site specific mutagenesis, generating MHC class I molecules lacking these cysteines, and demonstrated that their expression on the cell surface was impaired. Surprisingly, we demonstrated that these cysteines are crucial for the surface binding of the leukocyte Ig-like receptor 1 inhibitory receptor to the MHC class I proteins, but not for the binding of the KIR2DL1 inhibitory receptor. In addition, we demonstrated that the cysteine residues in the cytoplasmic tail of MHC class I proteins are crucial for their egress from the endoplasmic reticulum and for their palmitoylation, thus probably affecting their expression on the cell surface. Finally, we show that the cysteine residues are important for proper extracellular conformation. Thus, although the interaction between leukocyte Ig-like receptor 1 and MHC class I proteins is formed between two extracellular surfaces, the intracellular components of MHC class I proteins play a crucial role in this recognition.
- Subjects :
- Amino Acid Sequence
Cell Line, Transformed
Cell Membrane genetics
Cell Membrane immunology
Cysteine genetics
Cytotoxicity, Immunologic genetics
Extracellular Fluid metabolism
HLA-B7 Antigen biosynthesis
HLA-B7 Antigen genetics
HLA-B7 Antigen metabolism
HLA-C Antigens biosynthesis
HLA-C Antigens genetics
HLA-C Antigens metabolism
Humans
Killer Cells, Natural immunology
Molecular Sequence Data
Peptide Fragments biosynthesis
Peptide Fragments genetics
Peptide Fragments immunology
Peptide Fragments metabolism
Protein Conformation
Receptors, Immunologic antagonists & inhibitors
Receptors, Immunologic immunology
Receptors, KIR2DL1
Cysteine physiology
Extracellular Fluid immunology
HLA-B7 Antigen immunology
HLA-C Antigens immunology
Intracellular Fluid immunology
Intracellular Fluid metabolism
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 179
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17785801
- Full Text :
- https://doi.org/10.4049/jimmunol.179.6.3655