Peptides isolated from HLA-Cw*0304 confer different degrees of protection from natural killer cell-mediated lysis

Zappacosta, Francesca; Borrego, Francisco; Brööks, Andrëw G.; Parker, Kenneth C.; Coligan, John E.

doi:10.1016/s0165-2478(97)86397-3

Cited by 21 publications

(26 citation statements)

References 8 publications

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“…Binding of soluble KIR2DL1 to HLA-Cw4 only occurred when the MHC class I molecule was loaded with peptides, and certain substitutions at position 7 and 8 abolished the interaction [11]. HLA-Cw*0304 and -Cw7 interactions with KIR2DL2 were also modulated by the peptide present in the groove [12,16]. Similarly, we found that substitution at position 8 in the EBV EBNA3A peptide abolished binding to KIR3DL2.…”

Section: Substitution At Position 8 Abolishes Kir3dl2 Interaction Witsupporting

confidence: 62%

Recognition of HLA‐A3 and HLA‐A11 by KIR3DL2 is peptide‐specific

et al. 2004

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The recognition of MHC class I molecules by killer cell immunoglobulin-like receptors (KIR) is central to the control of NK cell function and can also modulate the CTL activation threshold. Among KIR receptors, KIR3DL2 is thought to interact with HLA-A3 and -A11, although direct evidence has been lacking. In this study, we show that HLA-A3 and -A11 tetramers specifically bind to KIR3DL2*001 transfectants and that this recognition is peptide-specific. Single amino acid substitutions in the nonamer peptide underline a critical role for residue 8 in recognition of KIR3DL2. However, the role of this interaction in vivo still remains to be established.

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Section: Substitution At Position 8 Abolishes Kir3dl2 Interaction Witsupporting

confidence: 62%

Recognition of HLA‐A3 and HLA‐A11 by KIR3DL2 is peptide‐specific

et al. 2004

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“…That Cw*0202 and Cw*0501 have identical contact residues for p8 and p9, the residues of the bound peptide that influences HLA-C interaction with KIR (32-34), suggests peptide effects could contribute to the broader and stronger binding reactions of these two HLA-C allotypes. Not all HLA-C-binding peptides are permissive to KIR interaction (35,36), raising the possibility that the differences we observe in the levels of saturation of KIR2D-Fc binding to the HLA-C allotypes is in part due to the different proportions of peptides they bind that are permissive to KIR interaction. Another possible cause of the differences is that the binding of anti-HLA class I mAb to beads does not correlate well with the accessibility of the KIR binding site on HLA-C because different allotypes tend to attach to the beads in different orientations.…”

Section: Direct Binding Assays Show Specific Interactions Of Kir2dl2 mentioning

confidence: 81%

Synergistic Polymorphism at Two Positions Distal to the Ligand-Binding Site Makes KIR2DL2 a Stronger Receptor for HLA-C Than KIR2DL3

Moesta

Norman²,

Yawata³

et al. 2008

The Journal of Immunology

344

468

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Interactions between HLA-C ligands and inhibitory killer cell Ig-like receptors (KIR) control the development and response of human NK cells. This regulatory mechanism is usually described by mutually exclusive interactions of KIR2DL1 with C2 having lysine 80, and KIR2DL2/3 with C1 having asparagine 80. Consistent with this simple rule, we found from functional analysis and binding assays to 93 HLA-A, HLA-B, and HLA-C isoforms that KIR2DL1*003 bound all C2, and only C2, allotypes. The allotypically related KIR2DL2*001 and KIR2DL3*001 interacted with all C1, but they violated the simple rule through interactions with several C2 allotypes, notably Cw*0501 and Cw*0202, and two HLA-B allotypes (B*4601 and B*7301) that share polymorphisms with HLA-C. Although the specificities of the “cross-reactions” were similar for KIR2DL2*001 and KIR2DL3*001, they were stronger for KIR2DL2*001, as were the reactions with C1. Mutagenesis explored the avidity difference between KIR2DL2*001 and KIR2DL3*001. Recombinant mutants mapped the difference to the Ig-like domains, where site-directed mutagenesis showed that the combination, but not the individual substitutions, of arginine for proline 16 in D1 and cysteine for arginine 148 in D2 made KIR2DL2*001 a stronger receptor than KIR2DL3*001. Neither residue 16 or 148 is part of, or near to, the ligand-binding site. Instead, their juxtaposition near the flexible hinge between D1 and D2 suggests that their polymorphisms affect the ligand-binding site by changing the hinge angle and the relative orientation of the two domains. This study demonstrates how allelic polymorphism at sites distal to the ligand-binding site of KIR2DL2/3 has diversified this receptor’s interactions with HLA-C.

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“…Such peptides may be produced in response to infection and introduce allosteric changes in HLA-C molecules or enhance the binding of HLA-C molecules by their cognate KIR receptor. Indeed, KIR preference for certain peptides sequences has been previously demonstrated in studies examining NK cell recognition of HLA-B27-expressing target cells (61,62) and in KIR2DL recognition of HLA-C molecules (63,64). However, we consider it unlikely that differential peptide recognition explains the better NK cell response conferred by the KIR2DL3/HLA-C1 compound genotype compared with the KIR2DL1/HLA-C2 compound genotype for the following reasons.…”

Section: Hla-c1 Homozygous and Hla-c2 Homozygous Groups Appearedmentioning

confidence: 88%