HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load.
Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B*1516 and HLA-B*1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection.
Frahm
Nicole
N
Partners AIDS Research Center, Massachusetts General Hospital, No. 5214, 149 13th Street, Charlestown, MA 02129, USA.
Adams
Sharon
S
Kiepiela
Photini
P
Linde
Caitlyn H
CH
Hewitt
Hannah S
HS
Lichterfeld
Mathias
M
Sango
Kaori
K
Brown
Nancy V
NV
Pae
Eunice
E
Wurcel
Alysse G
AG
Altfeld
Marcus
M
Feeney
Margaret E
ME
Allen
Todd M
TM
Roach
Timothy
T
St John
M Anne
MA
Daar
Eric S
ES
Rosenberg
Eric
E
Korber
Bette
B
Marincola
Francesco
F
Walker
Bruce D
BD
Goulder
Philip J R
PJ
Brander
Christian
C
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D018984:Epitopes, T-Lymphocyte; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen