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

FEBS Letters

Delmas, Agnès¹  Hsu, Shiou-Chih³  Trudelle, Yves¹  Abastado, Jean-Pierre²  Quesnel, Anne¹  Steward, Michael W.³ 

[1] Centre de Biophysigue Moleculaire, CNRS UPR 4301, rue Charles Sadron,45071 Orleans Cedex 2, France;Institut Pasteur, Unite de Biologie Moleculaire du Gene, INSERM U277, 25 rue du Dr Roux, 75724 Paris Cedex 15, France;Molecular Immunology Unit, Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London WCl E 7HT, UK

关键词: Major histocompatibility complex I;    Antigenic peptide;    Binding motif;    MHC affinity;    Cytotoxic T lymphocyte;    H-2Kd;    CHO;    Chinese hamster ovary;    CTL;    cytotoxic T lymphocyte;    ER;    endoplasmic reticulum;    FCS;    fetal calf serum;    HBSS;    Hank's balanced salt solution;    HPLC;    high-performance liquid chromatography;    IFA;    incomplete Freund's adjuvant;    mAb;    monoclonal antibody;    MALDI;    matrix-assisted laser desorption and ionization;    MHC;    major histocompatibility complex;    PBS;    phosphate-buffered saline;    TAP;    transporter associated with antigen processing;   

DOI  :  10.1016/0014-5793(96)00446-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Peptides eluted from the MHC class I K^d molecule are generally nonamers that display a strong preference for Tyr in position 2 and Ile or Len in position 9. We investigated the binding ability of several synthetic peptides which did not fit this consensus motif. In our peptides, Tyr² was substituted by other amino acids, i.e. Len, Ile or Met. These peptides were variants of the 252–260 K^d-restricted peptide SYIPSAEKI derived from the Plasmodium berghei circumsporozoite protein. They bound to purified K^d molecules in vitro with intermediate affinity. One of them was tested for in vivo stimulation of T cells and induced a cytotoxic response. These results demonstrate the importance of binding motif refinement to discover new binding characteristics and new ligands such as low-affinity peptides.

【 授权许可】

Unknown