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
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.