Extensive HLA class I allele promiscuity among viral CTL epitopes.
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.
Frahm
Nicole
N
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Yusim
Karina
K
Suscovich
Todd J
TJ
Adams
Sharon
S
Sidney
John
J
Hraber
Peter
P
Hewitt
Hannah S
HS
Linde
Caitlyn H
CH
Kavanagh
Daniel G
DG
Woodberry
Tonia
T
Henry
Leah M
LM
Faircloth
Kellie
K
Listgarten
Jennifer
J
Kadie
Carl
C
Jojic
Nebojsa
N
Sango
Kaori
K
Brown
Nancy V
NV
Pae
Eunice
E
Zaman
M Tauheed
MT
Bihl
Florian
F
Khatri
Ashok
A
John
Mina
M
Mallal
Simon
S
Marincola
Francesco M
FM
Walker
Bruce D
BD
Sette
Alessandro
A
Heckerman
David
D
Korber
Bette T
BT
Brander
Christian
C
D000483:Alleles; D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006678:HIV / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I
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