Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual.
HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/microl. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77-85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was recognized by HLA-A11-restricted CTL. Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the A11-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation.
Harrer
T
T
Department of Medicine III with Institute of Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. Thomas.Harrer@med3.med.uni-erlangen.de
Harrer
E
E
Barbosa
P
P
Kaufmann
F
F
Wagner
R
R
Brüggemann
S
S
Kalden
J R
JR
Feinberg
M
M
Johnson
R P
RP
Buchbinder
S
S
Walker
B D
BD
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000940:Antigenic Variation; D018791:CD4 Lymphocyte Count; D019556:COS Cells; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011533:Proviruses / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D019562:Viral Load; D014764:Viral Proteins; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1