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 histocompatibility complex (MHC) class I molecules. KIRs and T cell receptors (TCRs) bind in a peptide-dependent manner to overlapping regions of peptide-MHC class I complexes. KIRs with two immunoglobulin domains (KIR2Ds) recognize distinct subsets of HLA-C alleles. Here we use surface plasmon resonance to study the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide-HLA-Cw7 complexes. KIR2DL3 bound to the HLA-Cw7 allele presenting the peptide RYRPGTVAL with a 1:1 stoichiometry and an affinity (K(d) approximately 7 microM 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/HLA-Cw7, albeit with a 10-20-fold lower affinity. TCR/peptide-MHC interactions are characterized by comparatively slow kinetics and unfavorable entropic changes (Willcox, B. E., Gao, G. F., Wyer, J. R. , Ladbury, J. E., Bell, J. I., Jakobsen, B. K., and van der Merwe, P. A. (1999) Immunity 10, 357-365), suggesting that binding is accompanied by conformational adjustments. In contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association. These results indicate that KIR/peptide-MHC class I interactions have properties typical of other cell-cell recognition molecules, and they highlight the unusual nature of TCR/peptide-MHC recognition.
Maenaka
K
K
Structural Biology, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford OX3 7BN, United Kingdom. katsumi@strubi.ox.ac.uk
Juji
T
T
Nakayama
T
T
Wyer
J R
JR
Gao
G F
GF
Maenaka
T
T
Zaccai
N R
NR
Kikuchi
A
A
Yabe
T
T
Tokunaga
K
K
Tadokoro
K
K
Stuart
D I
DI
Jones
E Y
EY
van der Merwe
P A
PA
D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C515078:KIR2DL3 protein, human; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3