Identification and antigenicity of broadly cross-reactive and conserved human immunodeficiency virus type 1-derived helper T-lymphocyte epitopes.
Human immunodeficiency virus (HIV)-specific helper T lymphocytes (HTL) play a key role in the immune control of HIV type 1 (HIV-1) infection, and as such are an important target of potential HIV-1 vaccines. In order to identify HTL epitopes in HIV-1 that might serve as vaccine targets, conserved HIV-1-derived peptides bearing an HLA-DR binding supermotif were tested for binding to a panel of the most representative HLA-DR molecules. Eleven highly cross-reactive binding peptides were identified: three in Gag and eight in Pol. Lymphoproliferative responses to this panel of peptides, as well as to the HIV-1 p24 and p66 proteins, were evaluated with a cohort of 31 HIV-1-infected patients. All 11 peptides were recognized by peripheral blood mononuclear cells from multiple HIV-infected donors. Many of the responsive HIV-infected subjects showed recognition of multiple peptides, indicating that HIV-1-specific T-helper responses may be broadly directed in certain individuals. A strong association existed between recognition of the parental recombinant HIV-1 protein and the corresponding HTL peptides, suggesting that these peptides represent epitopes that are processed and presented during the course of HIV-1 infection. Lastly, responses to the supermotif peptides were mediated by CD4(+) T cells and were restricted by major histocompatibility complex class II molecules. The epitopes described herein are potentially important components of HIV-1 therapeutic and prophylactic vaccines.
Wilson
C C
CC
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Cara.Wilson@UCHSC.edu
Palmer
B
B
Southwood
S
S
Sidney
J
J
Higashimoto
Y
Y
Appella
E
E
Chesnut
R
R
Sette
A
A
Livingston
B D
BD
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D003429:Cross Reactions; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D006684:HLA-DR Antigens; D010455:Peptides