| Autor: |
Mason LH; Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Clinical Cancer Research, National Institutes of Health, Frederick, MD 21702-1201, USA. MasonL@mail.ncifcrf.gov, Willette-Brown J, Anderson SK, Alvord WG, Klabansky RL, Young HA, Ortaldo JR |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Oct 15; Vol. 171 (8), pp. 4235-42. |
| DOI: |
10.4049/jimmunol.171.8.4235 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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