Extensive HLA class I allele promiscuity among viral CTL epitopes
- Nicole Frahm ,
- Karina Yusim ,
- Todd J. Suscovich ,
- Sharon Adams ,
- John Sidney ,
- Peter Hraber ,
- Hannah S. Hewitt ,
- Caitlyn H. Linde ,
- Daniel G. Kavanagh ,
- Tonia Woodberry ,
- Leah M. Henry ,
- Kellie Faircloth ,
- Jennifer Listgarten ,
- Carl Kadie ,
- Nebojsa Jojic ,
- Kaori Sango ,
- Nancy V. Brown ,
- Eunice Pae ,
- M. Tauheed Zaman ,
- Florian Bihl ,
- Ashok Khatri ,
- Mina John ,
- Simon Mallal ,
- Francesco M. Marincola ,
- Bruce D. Walker ,
- Alessandro Sette ,
- David Heckerman ,
- Bette T. Korber ,
- Christian Brander
European Journal of Immunology | , Vol 37(9): pp. 2419-2433
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.