HUMAN CD4(-CELLS CAN DISCRIMINATE THE MOLECULAR AND STRUCTURAL CONTEXT OF T-EPITOPES OF HIV P66() T)

CD4(+) T cell lines and clones specific for human immunodeficiency vir us (HIV) antigens have been generated from peripheral lymphocytes of n aive individuals by priming with the envelope protein gp120. the enzym e reverse transcriptase (p66),and their synthetic peptides T cells wer e tested for proliferation to proteins to peptides, and to HIV virions . Different patterns of reaction were identified, T cells primed in vi tro with the whole antigen responded to the protein, but recognition o f overlapping peptides occurred with a fraction of the lines or clones . The virus was recognized by some; but not all, of the gp120- and p66 -specific T cells, with an efficiency 2 logs higher than the recombina nt soluble proteins on a molar basis. One T cell line specific for gp1 20 responded to virions presented by B cells, but not by monocytes. In contrast, T cells induced with peptides did not always respond to the proteins. Generation of T cell lines from naive individuals may be an in vitro model for T cell immunization, and the response patterns may have implications for the design of vaccines aimed at inducing a T he lper response. In fact our in vitro data suggest that (a) immunization with peptides does nor always induce T cells recognizing the whole pr otein, (b)immunization with proteins does not always induce T cells re cognizing the protein in the context of the HIV virus, and (c) recogni tion of gp120 in the context of HIV may be dictated by the type of pre senting cells.