MHC class I recognition by NK receptors in the Ly49 family is strongly influenced by the beta(2)-microglobulin subunit

Citation
J. Michaelsson et al., MHC class I recognition by NK receptors in the Ly49 family is strongly influenced by the beta(2)-microglobulin subunit, J IMMUNOL, 166(12), 2001, pp. 7327-7334
Citations number
52
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
166
Issue
12
Year of publication
2001
Pages
7327 - 7334
Database
ISI
SICI code
0022-1767(20010615)166:12<7327:MCIRBN>2.0.ZU;2-E
Abstract
NK cell recognition of targets is strongly affected by MHC class I specific receptors. The recently published structure of the inhibitory receptor Ly4 9A in complex with H-2D(d) revealed two distinct sites of interaction in th e crystal. One of these involves the alpha (1), alpha (2), alpha (3), and b eta (2)-microglobulin (beta (2)m) domains of the MHC class I complex. The d ata from the structure, together with discrepancies in earlier studies usin g MHC class I tetramers, prompted us to study the role of the beta (2)m sub unit in MHC class I-Ly49 interactions. Here we provide, to our knowledge, t he first direct evidence that residues in the beta (2)m subunit affect bind ing of MHC class I molecules to Ly49 receptors. A change from murine beta ( 2)m to human beta (2)m in three different MHC class I molecules, H-2D(b), H -2K(b), and H-2D(d), resulted in a loss of binding to the receptors Ly49A a nd Ly49C. Analysis of the amino acids involved in the binding of Ly49A to H -2D(d) in the published crystal structure, and differing between the mouse and the human beta (2)m, suggests the cluster formed by residues Lys(3), Th r(4), Thr(28), and Gln(29), as a potentially important domain for the Ly49A -H-2D(d) interaction. Another possibility is that the change of beta (2)m i ndirectly affects the conformation of distal parts of the MHC class I molec ule, including the alpha, and alpha (2) domains of the heavy chain.