Immunogenetics

, Volume 44, Issue 4, pp 233–241 | Cite as

Role of strong anchor residues in the effective binding of 10-mer and 11-mer peptides to HLA-A*2402 molecules

  • Masaaki Ibe
  • Yuki Ikeda Moore
  • Kiyoshi Miwa
  • Yutaro Kaneko
  • Shumpei Yokota
  • Masafumi Takiguchi
Original Paper
Received:
Revised:

Abstract

The binding capacity of one-hundred-and-seventy-two 8-mer to 11-mer peptides carrying HLA-A24 anchor residues to HLA-A*2402 molecules was analyzed by using a HLA class I stabilization assay. Most (76.2%) of these peptides bound to HLA-A*2402 molecules. These results confirmed previous findings that Tyr and Phe at P2 as well as Phe, Trp, Ile, and Leu at the C-terminus were main anchor residues for HLA-A*2402. Tyr at P2 was a stronger anchor residue than Phe, while bulky aromatic hydrophobic residues Phe and Trp at the C-terminus are stronger anchors than aliphatic hydrophobic residues Ile and Leu. These results were also supported by an analysis using a panel of mutated 9-mer peptides at P2 and P9. Taken together, these results suggest that HLA-A*2402 molecules have deep B- and F-pockets because they favor peptides carrying bulky aromatic hydrophobic residues at P2 and the C-terminus. The affinity of 8-mer peptides was significantly lower than that of 9-mer to 11-mer peptides, while there was no difference in affinity between 9-mer, 10-mer, and 11-mer peptides. The affinity of peptides carrying bulky aromatic hydrophobic residues at the C-terminus was higher than that of peptides carrying aliphatic hydrophobic residues in each of the 8-mer to 11-mer peptides, though the greatest difference in affinity was observed in 11-mer peptides. The strong interaction of side chains of these anchor residues with the corresponding pockets may permit the effective binding of 10-mer and 11-mer peptides to HLA-A*2402 molecules.

Keywords

Peptide Peptide Binding Mean Fluorescence Intensity Stabilization Assay Anchor Residue 
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References

  1. Chen, Y., Sideny, J., Southwood, S., Cox, A. L., Sakaguchi, K., Henderson, R. A., Appella, E., Hunt, D. F., Sette, A., and Engelhard, V. H. Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecules HLA-A2.1 with high affinity and in different conformations.J Immunol 152: 2874–2881, 1994PubMedGoogle Scholar
  2. Collins, E. J., Garboczi, D. N., and Wiley, D. C. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site.Nature 371: 626–629, 1994PubMedCrossRefGoogle Scholar
  3. Dai, L. C., West, K., Littaua, R., Takahashi, K., and Ennis, F. A. Mutation of human immunodeficiency virus type 1 at amino acid 585 on gp41 results in loss of killing by CD8+ A24-restricted cytotoxic T lymphocytes.J Virol 66: 3151–3154, 1992PubMedGoogle Scholar
  4. DiBrino, M., Parker, K. C., Shiloach, J., Turner, R. V., Tsuchida, T., Garfield, M., Biddison, W. E., and Coligan, J. E. Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8.J Immunol 152: 620–631, 1994PubMedGoogle Scholar
  5. Elivin, J., Cerundolo, V., Elliott, T., and Townsend A. A quantitative assay of peptide-dependent class I assembly.Eur J Immunol 21: 2025–2031, 1991CrossRefGoogle Scholar
  6. Engelhard, B. H. Structure of peptides associated with MHC class I molecules.Curr Opin Immunol 6: 13–23, 1994PubMedCrossRefGoogle Scholar
  7. Falk, K., Rötzschke, O., Stevanović, S., Jung, G., and Rammensee, H.-G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules.Nature 351: 290–296, 1991PubMedCrossRefGoogle Scholar
  8. Falk, K., Rötzschke, O., Grahovac, B., Schendel D., Stevanović, S., Jung, G., and Rammensee, H.-G. Peptide motifs of HLA-B35 and-B37 molecules.Immunogenetics 38: 161–162, 1993PubMedCrossRefGoogle Scholar
  9. Falk, K., Rötzschke, O., Takiguchi, M., Grahovac, B., Gnau, V., Stevanović, S., Jung, G., and Rammensee, H.-G. Peptide motifs of HLA-A1,-A11,-A31 and-A33 molecules.Immunogenetics 40: 238–241, 1994PubMedCrossRefGoogle Scholar
  10. Falk, K., Rötzschke, O., Takiguchi, M., Gnau, V., Stevanović, S., Jung, G., and Rammensee, H.-G. Peptide motifs of HLA-B51,-B52 and-B78 molecules, and implications for Behçet's disease.Int Immunol 7: 223–228, 1995PubMedCrossRefGoogle Scholar
  11. Jardetzky, T. S., Lane, W. S., Robinson, R. A., Madden, D. R., and Wiley, D. C. Identification of self peptides bound to purified HLA-B27.Nature 353: 326–329, 1991PubMedCrossRefGoogle Scholar
  12. Huczko, E. L., Bodnar, W. M., Benjamin, D., Sakaguchi, K., Zhu, N. Z., Shabanowitz, J., Henderson, R. A., Appella, E., Hunt, D. F., and Engelhard, V. H. Characteristics of endogenous peptides eluted from the class I MHC molecules HLA-B7 determined by mass spectrometry and computer modeling.J Immunol 151: 2572–2587, 1993PubMedGoogle Scholar
  13. Hunt, D. F., Henderson, R. A., Shabanowitz, J., Sakaguchi, K., Michel, H., Sevilir, N., Cox, A. L., Appella, E., and Engelhard, V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry.Science 255: 1261–1263, 1992PubMedCrossRefGoogle Scholar
  14. Kang, X., Kawakami, Y., El-Gamil, M., Wang, R., Sakaguchi, K., Yannelli, J. R., Appella, E., Rosenberg, S. A., and Robbins, P. F. Identification of tyrosinase epitopes recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes.J Immunol 155: 1343–1348, 1995PubMedGoogle Scholar
  15. Kikuchi, A., Sakaguchi, T., Miwa, K., Takamiya, Y., Rammensee, H.-G., Kaneko, Y., and Takiguchi, M. Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket.Immunogenetics 43: 268–276, 1996PubMedGoogle Scholar
  16. Kondo, A., Sidney, J., Southwood, S., del Guercio, M.-F., Appella, E., Sakamoto, H., Celis, E., Grey, H. M., Chesnut, R. W., Kubo, R. T., and Sette, A. Prominent roles of secondary anchor residues in peptide binding to HLA-A24 human class I molecules.J Immunol 155: 4307–4312, 1995PubMedGoogle Scholar
  17. Kubo, R. T., Sette, A., Grey, H. M., Appella, E., Sakaguchi, K., Zhu, N.-Z., Arnott, D., Sherman, N., Shabanowitz, J., Michel, H., Bodnar, W. M., Davis, T. A., and Hunt, D. F. Definition of specific peptide motifs for four major HLA-A alleles.J Immunol 152: 3913–3924, 1994PubMedGoogle Scholar
  18. Ljunggren, H.-G., Stam, N. J., Öhlén, C., Neefjes, J. J., Höglund, P., Heemels, M.-T., Bastin, J., Schumacher, T. N. M., Townsend, A., Kärre, K., and Ploegh, H. L. Empty MHC class I molecules come out in the cold.Nature 346: 476–480, 1990PubMedCrossRefGoogle Scholar
  19. Madden, D. R., Corga, J. C., Strominger, J. L., and Wiley, D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation.Nature 353: 321–325, 1991PubMedCrossRefGoogle Scholar
  20. Maier, R., Falk, K., Rötzschke, O., Maier, B., Gnau, V., Stevanović, S., Jung, G., Rammensee, H.-G., and Meyerhans, A. Peptide motifs of HLA-A3,-A24, and-B7 molecules as determined by pool sequencing.Immunogenetics 40: 306–308, 1994PubMedCrossRefGoogle Scholar
  21. Malcherek, G., Falk, K., Rötzschke, O., Rammensee, H.-G., Stevanović, S., Gnau, V., Jung, G., and Melms, A. Natural peptide ligand motifs of two HLA molecules associated with myasthenia gravis.Int Immunol 5: 1229–1237, 1993PubMedCrossRefGoogle Scholar
  22. Matsumura, M., Fremont, D. H., Peterson, P. A., and Wilson, I. A. Emerging principles for the recognition of peptide antigens by MHC class 1 molecules.Science 257: 927–934, 1992PubMedCrossRefGoogle Scholar
  23. Nokihara, K., Yamamoto, R., Hazama, M., Wakizawa, O., and Nakamura, S. Design and applications of a novel simultaneous multiple solid-phase peptide synthesizer.In R. Epton (ed.).Innovation and Perspectives in Solid-Phase Synthesis, pp. 445, Intercept, Andover, 1992Google Scholar
  24. Parker, K. C., Bednarek, M. A., Hull, L. K., Utz, Y., Cunningham, B., Zweerink, H. J., Biddison, W. E., and Coligan, J. E. Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2.J Immunol 149: 3580–3587 1992PubMedGoogle Scholar
  25. Rammensee, H.-G., Friede, T., and Stevanović, S. MHC lingands and peptide motifs: first listing.Immunogenetics 41: 178–228, 1995PubMedCrossRefGoogle Scholar
  26. Ruppert, J., Sidney, J., Celis, E., Kubo, R. T., Grey, H. M., and Sette, A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules.Cell 74: 929–937, 1993PubMedCrossRefGoogle Scholar
  27. Saper, M. A., Bjorkman, P. J., and Wiley, D. C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6Å resolution.J Med Biol 219: 277–319, 1991Google Scholar
  28. Schönbach, C., Ibe, M., Shiga, H., Takamiya, Y., Miwa, K., Nokihara, K., and Takiguchi, M. Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.J Immunol 154: 5951–5958, 1995PubMedGoogle Scholar
  29. Sidney, J., del Guercio, M.-F., Southwood, S., Engelhard, V. H., Appella, E., Rammensee, H.-G., Falk, K. Rötzschke, O., Takiguchi, M., Kubo, R. T., Grey, H. M., and Sette, A. Several HLA alleles share overlapping peptide specificities.J Immunol 154: 247–259, 1995PubMedGoogle Scholar
  30. Stuber, G., Modrow, S., Höglund, P., Franksson, L., Elvin, J., Wolf, H., Kärre, K., and Klein, G. Assessment of major histocompatibility complex class I interaction with Epstein-Barr virus and human immunodeficiency virus peptides by evaluation of membrane H-2 and HLA in peptide loading-deficient cells.Eur J Immunol 22: 2697–2703, 1992PubMedCrossRefGoogle Scholar
  31. Sutton, J., Rowland-Jones, S., Rosenberg, W., Nixon, D., Gotch, F., Gao, W.-M., Murray, N., Spoonas, A., Driscoll, P., Smith, M., Willis, A., and McMichael, A. A sequence pattern for peptides presented to cytotoxic T-lymphocytes by HLA-B8 revealed by analysis of epitopes and eluted peptides.Eur J Immunol 23: 447–453, 1993PubMedCrossRefGoogle Scholar
  32. Takamiya, Y., Schönbach, C., Nokihara, K., Ferrone, S., Yamaguchi, M., Kano, K., Egawa, K., and Takiguchi, M. HLA-B*3501-peptide interactions: role of anchor residues of peptides in their binding to HLA-B*3501 molecules.Int Immunol 6: 255–261, 1994PubMedCrossRefGoogle Scholar
  33. Udaka, K., Wiesmüller, K.-H., Kienle, S., Jung, G., and Walden, P. Decrypting the structure of major histocompatibility complex class I-restricted cytotoxic T lymphocyte epitopes with complex peptide libraries.J Exp Med 181: 2097–2108, 1995PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Masaaki Ibe
    • 1
  • Yuki Ikeda Moore
    • 1
  • Kiyoshi Miwa
    • 2
  • Yutaro Kaneko
    • 2
  • Shumpei Yokota
    • 3
  • Masafumi Takiguchi
    • 1
  1. 1.Department of Tumor Biology, Institute of Medical ScienceUniversity of TokyoTokyoJapan
  2. 2.Ajinomoto Central Research LaboratoryKawasaki, KanagawaJapan
  3. 3.Department of PediatricsYokohama City University, School of MedicineYokohama, KanagawaJapan

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