Human killer cell immunoglobulin (Ig)-1ike receptors (KIRs) are expressed on natural killer cells and some T cells, and regulate their cyiotoxicity by recognition of MHC class I on the target cells. KIRs consisting of two or three tandem lg domains in their extracellular regions (KIR2DS Or KIR3Ds) recognize HLA-C or -A,-B alleles, respectively. The E.co]j secretion system for the extracellular region of KlR2DL3 specific for HLA-Cwl,3,7 has been established and the crystals of KIR2DL3 were obtained. The crystal structure of KIR2DL3 specific for HLA-CW1, -Cw3, -Cw7 has been solved at 3A resolution. Comparison of the crystal structures of KIR2DL3 and KIR2DL1, which is specific for other HLA-C alleles, reveals a 23℃ difference in the unusually acute inter-domain elbow angle. The putative MHC class I binding site on KIR2D has some local conformational change derived from both domain reorientation and repacking in the core of the N-terminal domain. Surface plasmon resonance analysis of KIR2D/peptide-MHC class I interactions show that KIR and T cell receptor both recognize MHC class I with allele- and peptide-specificity, but show very different kinetic and thermodynamic characteristics.