title: Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.
abstract: 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.
authors.affiliation: AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brander
authors.forename: K E
authors.initials: KE
authors.lastname: Hartman
authors.forename: A K
authors.initials: AK
authors.lastname: Trocha
authors.forename: N G
authors.initials: NG
authors.lastname: Jones
authors.forename: R P
authors.initials: RP
authors.lastname: Johnson
authors.forename: B
authors.initials: B
authors.lastname: Korber
authors.forename: P
authors.initials: P
authors.lastname: Wentworth
authors.forename: S P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: S
authors.initials: S
authors.lastname: Wolinsky
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.forename: S A
authors.initials: SA
authors.lastname: Kalams
mesh_terms: 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*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens