The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer

J Exp Med. 2002 Oct 7;196(7):911-21. doi: 10.1084/jem.20020304.

Abstract

In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay. Natural 'deletion' of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4(+) HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4(+) HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4(+) HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • DNA Primers
  • HLA-B Antigens / immunology*
  • Humans
  • Jurkat Cells
  • Pan troglodytes
  • Polymerase Chain Reaction
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / immunology*
  • Receptors, KIR
  • Receptors, KIR3DL1
  • Recombinant Fusion Proteins / immunology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • DNA Primers
  • HLA-B Antigens
  • KIR3DL1 protein, human
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR3DL1
  • Recombinant Fusion Proteins