Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses.
Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or the strongest response within a single individual, yet factors determining either inter- or intraindividual immunodominance are still poorly understood. More than 90 individuals were tested against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes were significantly more frequently recognized than HLA-A- or HLA-C-restricted epitopes. HLA-B-restricted epitopes also induced responses of higher magnitude than did either HLA-A- or HLA-C-restricted epitopes, although this comparison only reached statistical significance for EBV epitopes. For both viruses, the magnitude and frequency of recognition were correlated with each other, but not with the epitope binding affinity to the restricting HLA allele. The presence or absence of HIV coinfection did not impact EBV epitope immunodominance patterns significantly. Peptide titration studies showed that the magnitude of responses was associated with high functional avidity, requiring low concentration of cognate peptide to respond in in vitro assays. The data support the important role of HLA-B alleles in antiviral immunity and afford a better understanding of the factors contributing to inter- and intraindividual immunodominance.
Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, 02129, USA.
Florian
F
Bihl
Nicole
N
Frahm
Loriana
L
Di Giammarino
John
J
Sidney
Mina
M
John
Karina
K
Yusim
Tonia
T
Woodberry
Kaori
K
Sango
Hannah S
HS
Hewitt
Leah
L
Henry
Caitlyn H
CH
Linde
John V
JV
Chisholm
Tauheed M
TM
Zaman
Eunice
E
Pae
Simon
S
Mallal
Bruce D
BD
Walker
Alessandro
A
Sette
Bette T
BT
Korber
David
D
Heckerman
Christian
C
Brander
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D000483:Alleles; D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D016056:Immunodominant Epitopes