Efficient binding to the MHC class I K<sup>d</sup> molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif

Quesnel, Anne; Hsu, Shiou-Chih; Delmas, A.F.; Steward, M. W.; Trudelle, Y.; Abastado, Jean-Pierre

doi:10.1016/0014-5793(96)00446-2

Cited by 9 publications

(15 citation statements)

References 21 publications

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“…These results have demonstrated the decisive role of anchor motifs in the binding of epitopes to MHC class I molecules. In contrast to this observation, previous studies have shown that many immunogenic and protective epitopes do not contain known anchor motifs 22,45,46 . In our experimental systems, exclusive of glycine (G), any substitution of known anchor motifs that reduced the binding of peptides to MHC class I molecules was still recognised by virus‐specific CD8 T lymphocytes for fewer IFN‐γ responses, for instance histidine (H) or cysteine (C) (Table 1; Figs 1c and 2a).…”

Section: Resultscontrasting

confidence: 90%

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

et al. 2012

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Summary MHC class I‐restricted CD8 T‐lymphocyte epitopes comprise anchor motifs, T‐cell receptor (TCR) contact residues and the peptide backbone. Serial variant epitopes with substitution of amino acids at either anchor motifs or TCR contact residues have been synthesized for specific interferon‐γ responses to clarify the TCR recognition mechanism as well as to assess the epitope prediction capacity of immunoinformatical programmes. CD8 T lymphocytes recognise the steric configuration of functional groups at the TCR contact side chain with a parallel observation that peptide backbones of various epitopes adapt to the conserved conformation upon binding to the same MHC class I molecule. Variant epitopes with amino acid substitutions at the TCR contact site are not recognised by specific CD8 T lymphocytes without compromising their binding capacity to MHC class I molecules, which demonstrates two discrete antigen presentation events for the binding of peptides to MHC class I molecules and for TCR recognition. The predicted outcome of immunoinformatical programmes is not consistent with the results of epitope identification by laboratory experiments in the absence of information on the interaction with TCR contact residues. Immunoinformatical programmes based on the binding affinity to MHC class I molecules are not sufficient for the accurate prediction of CD8 T‐lymphocyte epitopes. The predictive capacity is further improved to distinguish mutant epitopes from the non‐mutated epitopes if the peptide–TCR interface is integrated into the computing simulation programme.

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Section: Resultscontrasting

confidence: 90%

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

et al. 2012

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“…Interdependent pairs of amino acids at P 2 and P C-2 meant these anchor positions could be occupied by amino acids with very different sizes and chemical properties. There are several examples in which pool sequences have not led to consistent motifs or in which single peptides that bind an MHC class I molecule did not fit the motif (Gaddum et al, 1996;Quesnel et al, 1996;Mata et al, 1998; human nonclassical MHC class I molecules HLA-E (1KPR, 1KTL, 1MHE, and 2ESV, light violet) and HLA-G (1YDP, 2DYP, and 2D31, wine red), and the rat MHC class I molecule RT1-A (1KJV, brown). The 10-mer and 11-mer peptides are highlighted as thicker lines.…”

Section: Discussionmentioning

confidence: 98%

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

et al. 2007

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Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.

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“…There are already many such examples in the literature, on this subject, and, in some cases, these unusual peptides are essential for host defense (20). Therefore, a search for class I-restricted antigenic peptides should not be limited to peptides displaying canonical binding motifs, especially in the case of tumor antigens (21). The identified R9M junction peptide being nonself, induction or reinforcement of R9M-specific CTL responses should not be harmful for the host.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Yotnda¹,

Garcı́a²,

Grandchamp³

et al. 1998

J. Clin. Invest.

104

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Efficient binding to the MHC class I K^d molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif

Cited by 9 publications

References 21 publications

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

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Efficient binding to the MHC class I Kd molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif

Cited by 9 publications

References 21 publications

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

Steric recognition of T‐cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

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Efficient binding to the MHC class I K^d molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif