Identification of a conserved universal Th epitope in HIV-1 reverse transcriptase that is processed and presented to HIV-specific CD4+ T cells by at least four unrelated HLA-DR molecules.
CD4+ Th cells play an important role in the induction and maintenance of specific T cell immunity. Indications for a protective role of CD4+ T cells against HIV-1 infection were found in subjects who were able to control HIV-1 viremia as well as in highly HIV-1-exposed, yet seronegative, individuals. This study describes the identification of an HIV-1-specific Th epitope that exhibits high affinity binding as well as high immunogenicity in the context of at least four different HLA-DR molecules that together cover 50-60% of the Caucasian, Oriental, and Negroid populations. This HIV-1 reverse transcriptase-derived peptide (RT171-190) is highly conserved among different HIV-1 isolates. Importantly, stimulation of PBL cultures from HIV-1 seronegative donors with this peptide resulted in Thl-type lymphocytes capable of efficient recognition of HIV-1-pulsed APCs. Taken together, these data indicate that peptide RT171-190 constitutes an attractive component of vaccines aiming at induction or enhancement of HIV-1-specific T cell immunity.
van der Burg
S H
SH
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands. shvdburg@worldonline.nl
Kwappenberg
K M
KM
Geluk
A
A
van der Kruk
M
M
Pontesilli
O
O
Hovenkamp
E
E
Franken
K L
KL
van Meijgaarden
K E
KE
Drijfhout
J W
JW
Ottenhoff
T H
TH
Melief
C J
CJ
Offringa
R
R
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000821:virology; D002999:Clone Cells; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology* / Q000821:virology
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D010455:Peptides; D054303:HIV Reverse Transcriptase