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Characterization of a Putative Receptor Binding Surface on Skint-1, a Critical Determinant of Dendritic Epidermal T Cell Selection.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2016 Apr 22; Vol. 291 (17), pp. 9310-21. Date of Electronic Publication: 2016 Feb 25. - Publication Year :
- 2016
-
Abstract
- Dendritic epidermal T cells (DETC) form a skin-resident γδ T cell population that makes key contributions to cutaneous immune stress surveillance, including non-redundant contributions to protection from cutaneous carcinogens. How DETC become uniquely associated with the epidermis was in large part solved by the identification of Skint-1, the prototypic member of a novel B7-related multigene family. Expressed only by thymic epithelial cells and epidermal keratinocytes, Skint-1 drives specifically the development of DETC progenitors, making it the first clear candidate for a selecting ligand for non-MHC/CD1-restricted T cells. However, the molecular mechanisms underpinning Skint-1 activity are unresolved. Here, we provide evidence that DETC selection requires Skint-1 expression on the surface of thymic epithelial cells, and depends upon specific residues on the CDR3-like loop within the membrane-distal variable domain of Skint-1 (Skint-1 DV). Nuclear magnetic resonance of Skint-1 DV revealed a core tertiary structure conserved across the Skint family, but a highly distinct surface charge distribution, possibly explaining its unique function. Crucially, the CDR3-like loop formed an electrostatically distinct surface, featuring key charged and hydrophobic solvent-exposed residues, at the membrane-distal tip of DV. These results provide the first structural insights into the Skint family, identifying a putative receptor binding surface that directly implicates Skint-1 in receptor-ligand interactions crucial for DETC selection.<br /> (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Animals
Cell Line
Humans
Mice
Nuclear Magnetic Resonance, Biomolecular
Protein Structure, Quaternary
Protein Structure, Secondary
Epidermis immunology
Epithelial Cells immunology
Immunoglobulins chemistry
Immunoglobulins immunology
Receptors, Antigen, T-Cell, gamma-delta immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 291
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26917727
- Full Text :
- https://doi.org/10.1074/jbc.M116.722066