Killer cell immunoglobulin receptors and T cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties

Human natural killer cells and a subset of T cells express a repertoire of killer cell immunoglobulin receptors (KIRs) that recognize major histocompa tibility complex (MHC) class I molecules. KIRs and T cell receptors (TCRs) bind in a peptide-dependent manner to overlapping regions of peptide-MHC cl ass I complexes. KIRs with two immunoglobulin domains (KIR2Ds) recognize di stinct subsets of HLA-C alleles. Here we use surface plasmon resonance to s tudy the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide -HLA-Cw7 complexes. KIR2DL3 bound to the HLA-Cw7 allele presenting the pept ide RYRPGTVAL with a 1:1 stoichiometry and an affinity (K-d similar to 7 mu M at 25 degrees C) within the range of values measured for other cell-cell recognition molecules, including the TCR. Although KIR2DL1 is reported not to recognize the HLA-Cw7 allele in functional assays, it bound RYRPGTVAL/H LA-Cw7, albeit with a 10-20-fold lower affinity. TCR/peptide-MHC interactio ns are characterized by comparatively slow kinetics and unfavorable entropi c changes (Willcox, B. E., Gao, G. F., WS er, J. R., Ladbury, J. E., Bell, J. I., Jakobsen, B. K,, and van der Merwe, P. A. (1999) Immunity 10, 357-36 5), suggesting that binding is accompanied by conformational adjustments. I n contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association. T hese results indicate that KIR/peptide-MHC class I interactions have proper ties typical of other cell-cell recognition molecules, and they highlight t he unusual nature of TCR/peptide-MHC recognition.