Peptide Specificity in the Recognition of MHC Class I by Natural Killer Cell Clones

Malnati, Mauro S.; Peruzzi, Marta; Parker, Kenneth C.; Biddison, William E.; Ciccone, Ermanno; Moretta, Alessandro; Long, Eric O.

doi:10.1126/science.7863326

Cited by 291 publications

(197 citation statements)

References 30 publications

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“…Peptide specificity in the recognition of MHC class I by NK cell clones has previously been reported for inhibitory KIR receptors. HLA-B*2705 interaction with KIR3DL1 shows some degree of peptide specificity, with residues at positions 7 and 8 identified as critical for the recognition [10,15]. 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].…”

Section: Substitution At Position 8 Abolishes Kir3dl2 Interaction Witmentioning

confidence: 99%

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 Witmentioning

confidence: 99%

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

et al. 2004

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“…Binding of the KIR3DL1 receptor to the Bw4 family of MHC class 1 receptors has been shown to be dependent both on key residues of the a-1 helix around Ile80, and also on bound peptide [18]. Peruzzi et al studied NK recognition of B*2705-transfected RMAS cells loaded with peptide analogues of a (protective) self-peptide FRYNGLIHR, and showed that substitution of the P7I for A, D or R reduced protection from lysis [20].…”

Section: Kir3dl1 Sensitivity To the Ebv Peptide P8 Side Chainmentioning

confidence: 99%

“…Evidence indicates that KIR3DL1 binds the MHC a1 helix around residues 76-80, with specificity for all Bw4 alleles containing threonine at heavy-chain residue 80 [17]. In the case of HLA-B*2705 at least, KIR3DL1 also has specificity for bound peptide, showing greatest sensitivity for the residue at position 8 [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

et al. 2005

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We have solved the crystal structures of three HLA‐B*2705–peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258–266 (RRIYDLIEL), influenza (flu) nucleoprotein NP383–391 (SRYWAIRTR), and HIV gag 264–273 (KRWIILGLNK). Long‐term non‐progression during HIV infection has been associated with presentation by HLA‐B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen‐bonding network observed between the HLA‐B*2705 B‐pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent‐exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA‐B*2705 complex with flu NP383–391, the amino acid side chains of residues 4, 7 and 8 are solvent‐exposed whilst in the HIV decamer, the main‐chain bulges into the solvent around P7. Thus, HLA‐B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA‐B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer‐Ig‐like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA‐B*2705–EBV structure the P8 glutamate side chain is solvent‐exposed and may inhibit KIR3DL1 binding through electrostatic forces.See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425875

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“…Viral peptides modulate recognition of HLA-B27 by NK receptors KIR3DL1 recognizes HLA-B*2705, interacting with residues around position 80, and with peptide residues 7 and 8 [24][25][26]. The crystal structure of this receptor is not known, but its interaction with B*2705 can be inferred from the structures of the KIR2DL2-HLA-Cw3 and KIR2DL1-HLA-Cw4 complexes [27,28].…”

Section: Hla-b27 Binding and Antigenic Features Of Immunodominant Virmentioning

confidence: 99%

HLA‐B27: portraying immunodominant viral epitopes

Castro

2005

Eur J Immunol

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Although the crystal structure of HLA-B27 has been known for a long time, only recently have X-ray diffraction studies of this molecule in complex with individual peptides become available. The report of three such structures involving viral epitopes that are immunodominant in HLA-B27-restricted T cell responses against influenza, EpsteinBarr and HIV viruses significantly improves our perception of critical aspects of the immunological and pathogenetic roles of HLA-B27, including (1) the molecular basis of its peptide-binding specificity and how this is modulated by subtype polymorphism, (2) the relationship between the structural and the antigenic features of immunodominant viral epitopes, (3) the basis for long term non-progression to AIDS of HIV-infected HLA-B27 + individuals, and (4) the structural features of microbial peptides influencing NK receptor engagement. Here, I discuss the implications of this and related studies for the relevance of HLA-B27 in host defense and as a pathogenetic molecule in spondyloarthritis.

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Peptide Specificity in the Recognition of MHC Class I by Natural Killer Cell Clones

Cited by 291 publications

References 30 publications

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

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

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

HLA‐B27: portraying immunodominant viral epitopes

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