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

Anne Quesnel (1) , Shiou-Chih Hsu (2) , Agnès F. Delmas (1) , Michael Steward (2) , Yves Trudelle (1) , Jean-Pierre Abastado (3)

1 CBM - Centre de biophysique moléculaire
2 LSHTM - London School of Hygiene and Tropical Medicine
3 Biologie Moléculaire du Gène

Peptides eluted from the MHC class I Kd 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 Kd‐restricted peptide SYIPSAEKI derived from the Plasmodium berghei circumsporozoite protein. They bound to purified Kd 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.

Mots clés: 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; Major histocompatibility complex I; Antigenic peptide; Binding motif; MHC affinity; Chinese hamster ovary; cytotoxic T lymphocyte; endoplasmic reticulum; HBSS Hank's balanced salt solution; HPLC high-performance liquid chromatography

Domaines: Sciences du Vivant [q-bio]

Anne Quesnel, Shiou-Chih Hsu, Agnès F. Delmas, Michael Steward, Yves Trudelle, et al.. 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. FEBS Letters, 1996, 387 (1), pp.42-46. ⟨10.1016/0014-5793(96)00446-2⟩. ⟨hal-02146830⟩