Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.
Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.
Brander
C
C
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Hartman
K E
KE
Trocha
A K
AK
Jones
N G
NG
Johnson
R P
RP
Korber
B
B
Wentworth
P
P
Buchbinder
S P
SP
Wolinsky
S
S
Walker
B D
BD
Kalams
S A
SA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D002908:Chronic Disease; D000939:Epitopes; D015497:HIV-1; D015234:HLA-A Antigens / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015234:HLA-A Antigens