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 HN type I (HIV-1) infection, and as su ch are an important target of potential HIV-I vaccines. In order to identif y HTL epitopes in HIV-1 that might serve as vaccine targets, conserved HN-l -derived peptides bearing an HLA-DR binding supermotif were tested for bind ing to a panel of the most representative HLA-DR molecules. Eleven highly c ross-reactive binding peptides were identified: three in Gag and eight in P ol. 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-l-in fected patients. All 11 peptides were recognized by peripheral blood mononu clear cells from multiple HIV-infected donors. Many of the responsive HIV-i nfected subjects showed recognition of multiple peptides, indicating that H IV-l-specific T-helper responses may be broadly directed in certain individ uals. A strong association existed between recognition of the parental reco mbinant HIV-1 protein and the corresponding HTL peptides, suggesting that t hese peptides represent epitopes that are processed and presented during th e course of HIV-I infection. Lastly, responses to the supermotif peptides w ere mediated by CD4(+) T cells and were restricted by major histocompatibil ity complex class II molecules. The epitopes described herein are potential ly important components of HIV-1 therapeutic and prophylactic vaccines.