Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis

✍ Scribed by Katja E. Andersson; Geoffrey S. Williams; Daniel M. Davis; Petter Höglund

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 372 KB
• Volume: 37
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200636693

✦ Synopsis

Abstract

Murine natural killer (NK) cells are inhibited by target cell MHC class I molecules via Ly49 receptors. However, Ly49 receptors can be made inaccessible to target cell MHC class I by a cis interaction with its MHC class I ligand within the NK cell membrane. It has recently been demonstrated that MHC class I proteins transfer from the target cells to the NK cell. Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface. Ly49A^+^ NK cells from mice expressing the Ly49A ligand H‐2D^d^ showed a 90% reduction in Ly49A accessibility compared to Ly49A^+^ NK cells from H‐2D^d^‐negative mice. The reduction was caused both by lower expression of Ly49A and interactions in cis between Ly49A and H‐2D^d^ at the NK cell surface. Approximately 75% of the Ly49A receptors on H‐2D^d^‐expressing NK cells were occupied in cis with endogenous H‐2D^d^ and only 25% were free to interact with H‐2D^d^ molecules in trans. Thus, H‐2D^d^ ligands control Ly49A receptor accessibility through interactions both in cis and in trans.