Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815

Van den Eynde, Benoit;Mazarguil, Honoré;Lethé, Bernard;Laval, Françoise;Gairin, Jean-Edouard
(1994) European Journal of Immunology — Vol. 24, n° 11, p. 2740-2745 (1994)

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  • Van den Eynde, Benoitorcid-logoUCLouvain
    Author
  • Mazarguil, HonoréUCLouvain
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  • Lethé, BernardUCLouvain
    Author
  • Laval, FrançoiseUCLouvain
    Author
  • Gairin, Jean-EdouardUCLouvain
    Author
Abstract
Mouse mastocytoma P815 expresses tumor antigens P815A and P815B encoded by a single gene called P1A and carried by a single peptide named P1A 35-43 (NH2-Leu-Pro-Tyr-Leu-Gly-Trp-Leu-Val-Phe-COOH). P1A 35-43 is presented to anti-P815A and anti-P815B cytotoxic T lymphocytes (CTL) by major histocompatibility complex (MHC) H-2Ld molecules. In order to determine the individual role played by each amino acid residue of P1A 35-43 in binding to H-2Ld and in recognition by anti-A and anti-B T cell receptors (TcR), a series of P1A35-43 peptides substituted by alanine at single positions was synthesized and tested for binding to H-2Ld and for CTL recognition. Binding to H-2Ld was estimated by measuring the ability of the peptide to up-regulate cell surface expression of H-2Ld. We found that three residues were important for interaction of P1A 35-43 with H-2Ld. Two of them, Pro at position 2 and Phe at position 9 were consistent with the described H-2Ld binding motif. A third residue, Trp at position 6, was also required for effective MHC binding of the tumor antigen. CTL sensitization assays showed that alanine substitution at position 7 (Leu) or at position 8 (Val) dramatically affected peptide recognition by anti-A CTL while positions 3 (Tyr) and 4 (Leu) were critical for recognition by anti-B CTL. We conclude that Pro2, Trp6 and Phe9 constitute the anchor residues of P1A 35-43 to H-2Ld, whereas the dipeptidyl sequences Tyr3-Leu4 and Leu7-Val8 form the core epitopes recognized by the TcR of anti-P815B and anti-P815A CTL, respectively.
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Van den Eynde, B., Mazarguil, H., Lethé, B., Laval, F., & Gairin, J.-E. (1994). Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815. European Journal of Immunology, 24(11), 2740-2745. https://doi.org/10.1002/eji.1830241125 (Original work published 1994)