Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif.
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to assess in immunogenicity studies in infected persons and in uninfected recipients of candidate HIV-1 vaccines.
Altfeld
M A
MA
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Livingston
B
B
Reshamwala
N
N
Nguyen
P T
PT
Addo
M M
MM
Shea
A
A
Newman
M
M
Fikes
J
J
Sidney
J
J
Wentworth
P
P
Chesnut
R
R
Eldridge
R L
RL
Rosenberg
E S
ES
Robbins
G K
GK
Brander
C
C
Sax
P E
PE
Boswell
S
S
Flynn
T
T
Buchbinder
S
S
Goulder
P J
PJ
Walker
B D
BD
Sette
A
A
Kalams
S A
SA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D001665:Binding Sites; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D016336:Gene Products, vpr / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000502:physiology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D016336:Gene Products, vpr; D015789:HLA-A2 Antigen; D054325:vpr Gene Products, Human Immunodeficiency Virus