Abstract |
Murine NK cells express the Ly-49 family of class I MHC-binding receptors that control their ability to lyse tumor or virally infected host target cells. X-ray crystallography studies have identified two predominant contact sites (sites 1 and 2) that are involved in the binding of the inhibitory receptor, Ly-49A, to H-2D(d). Ly-49G2 (inhibitory) and Ly-49D (activating) are highly homologous to Ly-49A and also recognize H-2D(d). However, the binding of Ly-49D and G(2) to H-2D(d) is of lower affinity than Ly-49A. All Ly-49s contain N-glycosylation motifs; however, the importance of receptor glycosylation in Ly-49-class I interactions has not been determined. Ly-49D and G(2) contain a glycosylation motif (NTT (221-223)), absent in Ly-49A, adjacent to one of the proposed binding sites for H-2D(d) (site 2). The presence of a complex carbohydrate group at this critical site could interfere with class I binding. In this study, we are able to demonstrate for the first time that Ly-49D binds H-2D(d) in the presence of mouse beta(2)-microglobulin. We also demonstrate that glycosylation of the NTT (221-23) motif of Ly-49D inteferes with recognition of H-2D(d). Alteration of the Ly-49D-NTT (221-23) motif to abolish glycosylation at this site resulted in enhanced H-2D(d) binding and receptor activation. Furthermore, glycosylation of Ly-49G2 at NTT (221-23) also reduces receptor binding to H-2D(d) tetramers. Therefore, the addition of complex carbohydrates to the Ly-49 family of receptors may represent a mechanism by which NK cells regulate affinity for host class I ligands.
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Authors | Llewellyn H Mason, Jami Willette-Brown, Stephen K Anderson, W Gregory Alvord, Richard L Klabansky, Howard A Young, John R Ortaldo |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 171
Issue 8
Pg. 4235-42
(Oct 15 2003)
ISSN: 0022-1767 [Print] United States |
PMID | 14530347
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, Ly
- Cross-Linking Reagents
- H-2 Antigens
- Histocompatibility Antigen H-2D
- Histocompatibility Antigens Class I
- Interleukin-2
- Lectins, C-Type
- Receptors, Immunologic
- Receptors, NK Cell Lectin-Like
- Arginine
- Ribonucleases
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Topics |
- Amino Acid Motifs
(genetics, immunology)
- Amino Acid Sequence
- Amino Acid Substitution
(genetics, immunology)
- Animals
- Antigens, Ly
(genetics, metabolism)
- Arginine
(genetics, metabolism)
- Cross-Linking Reagents
(metabolism)
- Gene Targeting
- Glycosylation
- H-2 Antigens
(metabolism)
- Histocompatibility Antigen H-2D
- Histocompatibility Antigens Class I
(metabolism)
- Humans
- Interleukin-2
(metabolism)
- Jurkat Cells
- Lectins, C-Type
- Mice
- Molecular Sequence Data
- Mutagenesis, Site-Directed
- Protein Binding
(genetics, immunology)
- Receptors, Immunologic
(genetics, immunology, metabolism)
- Receptors, NK Cell Lectin-Like
- Ribonucleases
(genetics)
- Transfection
- Up-Regulation
(genetics, immunology)
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