Helper T-cell recognition of HIV-1 Tat synthetic peptides

The regulatory proteins coded by the human immunodeficiency virus, (HIV)-1 genome are expressed by the infected cells before the initiation of the synthesis of structural proteins and thus immune response directed against these proteins could destroy infected cells before the release of infectious virions. The evaluation of T-lymphocyte responses toward Tat, one of the main HIV-1 regulatory proteins, is therefore of interest. We selected a group of HIV-infected patients with retained response to the recall antigen purified protein derivative and tested their CD4+ helper T-cell response toward recombinant Tat and toward 12 soluble synthetic partially overlapping 15-16-mer Tat peptides in a proliferation assay. Three peptides (amino acids 17-32, 33-48, and 65-80) were significantly recognized by the helper T-cells from infected individuals but not by the nine HIV-1-negative control persons. Nine of the 14 patients (64%) responded to at least one of these Tat peptides. Of the identified immunodominant peptides containing T-cell epitopes, one (aa 65-80) was recognized in association with human leukocyte antigens DR-2 allele, while the others appeared to be promiscuous and were equally recognized in association with several DR molecules. The identified immunogenic peptides were analyzed for the predicted presence of T-cell antigenic sites by several algorithms and positive correlation was detected for each peptide. Our results thus indicate that Tat protein can induce a cell-mediated immune response and identify three peptides containing T-cell epitopes that may be of importance in vaccine development.