A region of the third variable loop of HIV-1 gp120 is recognized by HLA-B7-restricted CTLs from two acute seroconversion patients.
HIV-1 envelope-specific CTL clones were isolated from the peripheral blood of two patients from within weeks of seroconversion. These clones were CD8+ and restricted by the HLA-B7 molecule. The minimum epitope recognized by the clones was determined to be the 30-amino acid (aa) sequence RPNNNTRKSI within the third variable (V3) loop of the envelope glycoprotein gp120. The aa sequence of this epitope is consistent with the motif found in naturally processed peptides eluted from HLA-B7 molecules. This region of the V3 loop is reasonably well conserved among clade B and some nonclade B isolates of HIV-1, especially at the anchor residues that determine binding to the HLA-B7 molecule. Using peptides based upon virus sequences present within each patient, we determined that autologous viruses were recognized by the clones, and we detected no escape variants from the initial clonal response during the acute phase of infection. Interestingly, a serine to arginine change at position 9 of the epitope abrogated clone recognition in one of the patients. This aa change is one factor that has been associated with a change from a nonsyncytium-inducing to a syncytium-inducing phenotype of HIV-1, raising the possibility that in HLA-B7-expressing patients, escape from this clonal CTL response and a change in viral phenotype may be linked. This study demonstrates that human CTL can be generated against sequences within the third variable loop of HIV-1 gp120. Because multiple vaccine strategies are based upon the V3 loop of HIV-1 gp120, this defined epitope can be exploited in determining the ability of certain vaccines to stimulate a CTL response in a select population of individuals.
Safrit
J T
JT
Aaron Diamond AIDS Research Center and the Department of Medicine and Microbiology, New York University, School of Medicine, New York 10016.
Lee
A Y
AY
Andrews
C A
CA
Koup
R A
RA
D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D018604:Epitope Mapping; D000939:Epitopes; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D017931:DNA Primers; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015793:HLA-B7 Antigen