Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes.
Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations.
Frahm
Nicole
N
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kiepiela
Photini
P
Adams
Sharon
S
Linde
Caitlyn H
CH
Hewitt
Hannah S
HS
Sango
Kaori
K
Feeney
Margaret E
ME
Addo
Marylyn M
MM
Lichterfeld
Mathias
M
Lahaie
Matthew P
MP
Pae
Eunice
E
Wurcel
Alysse G
AG
Roach
Timothy
T
St John
M Anne
MA
Altfeld
Marcus
M
Marincola
Francesco M
FM
Moore
Corey
C
Mallal
Simon
S
Carrington
Mary
M
Heckerman
David
D
Allen
Todd M
TM
Mullins
James I
JI
Korber
Bette T
BT
Goulder
Philip J R
PJ
Walker
Bruce D
BD
Brander
Christian
C
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D015331:Cohort Studies; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics; D059910:HLA-B15 Antigen; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; D016056:Immunodominant Epitopes