Cellular immune response

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Extensive HLA class I allele promiscuity among viral CTL epitopes

  1. Nicole Frahm1,
  2. Karina Yusim2,
  3. Todd J. Suscovich1,
  4. Sharon Adams3,
  5. John Sidney4,
  6. Peter Hraber2,
  7. Hannah S. Hewitt1,
  8. Caitlyn H. Linde1,
  9. Daniel G. Kavanagh1,
  10. Tonia Woodberry1,
  11. Leah M. Henry1,
  12. Kellie Faircloth1,
  13. Jennifer Listgarten5,
  14. Carl Kadie5,
  15. Nebojsa Jojic5,
  16. Kaori Sango1,
  17. Nancy V. Brown1,
  18. Eunice Pae6,
  19. M. Tauheed Zaman7,
  20. Florian Bihl1,
  21. Ashok Khatri8,
  22. Mina John9,
  23. Simon Mallal9,
  24. Francesco M. Marincola3,
  25. Bruce D. Walker1,10,
  26. Alessandro Sette4,
  27. David Heckerman5,
  28. Bette T. Korber2,11,
  29. Christian Brander1,*

Article first published online: 17 AUG 2007

DOI: 10.1002/eji.200737365

Issue

European Journal of Immunology

European Journal of Immunology

Volume 37, Issue 9, pages 2419–2433, September 2007

Additional Information

How to Cite

Frahm, N., Yusim, K., Suscovich, Todd J., Adams, S., Sidney, J., Hraber, P., Hewitt, Hannah S., Linde, Caitlyn H., Kavanagh, Daniel G., Woodberry, T., Henry, Leah M., Faircloth, K., Listgarten, J., Kadie, C., Jojic, N., Sango, K., Brown, Nancy V., Pae, E., Zaman, M. Tauheed., Bihl, F., Khatri, A., John, M., Mallal, S., Marincola, Francesco M., Walker, Bruce D., Sette, A., Heckerman, D., Korber, Bette T. and Brander, C. (2007), Extensive HLA class I allele promiscuity among viral CTL epitopes. Eur. J. Immunol., 37: 2419–2433. doi: 10.1002/eji.200737365

Author Information

  1. 1

    Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

  2. 2

    Theoretical Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA

  3. 3

    Clinical Center NIH, Bethesda, MD, USA

  4. 4

    La Jolla Institute of Allergy and Immunology, La Jolla, CA, USA

  5. 5

    Microsoft Research, Redmond, WA, USA

  6. 6

    Fenway Community Health Center, Boston, MA, USA

  7. 7

    Lemuel Shattuck Hospital, Boston, MA, USA

  8. 8

    Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

  9. 9

    Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia

  10. 10

    Howard Hughes Medical Institute, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA, USA

  11. 11

    Santa Fe Institute, Santa Fe, NM, USA

*Partners AIDS Research Center, Massachusetts General Hospital/Harvard Medical School, 149 13th Street, Room 5239, Charlestown, MA 02129, USA, Fax: +1-617-726-5345

Publication History

  1. Issue published online: 27 AUG 2007
  2. Article first published online: 17 AUG 2007
  3. Manuscript Accepted: 16 JUL 2007
  4. Manuscript Revised: 30 MAY 2007
  5. Manuscript Received: 5 APR 2007

Funded by

  • NIH

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Keywords:

  • Antigen;
  • Bioinformatics;
  • CD8 T cells;
  • HIV;
  • Immune responses;
  • Presentation/processing

Abstract

Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals’ HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development.

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