The gp120 envelope of HIV-1 binds and presents peptides in a similar manner to human leukocyte antigen

We have previously reported that the conserved carboxy terminus of gp120 has a strong sequence and structural homology with the alpha helix of both HLA class I and II. Molecular modelling of gp120 suggests that, together with other reported conserved sequences that also contain HLA-like regions, the carboxy terminus could contribute to an overall structural homology with a putative binding site similar to that of DR1. In support of this, we have previously reported that specific antigenic photoreactive peptides could crosslink to gp120 in a similar manner to DR1, and the crosslinking was saturable by excess antigenic peptides. We now report evidence that the gp120 enveloped peptide complex can be recognized in a similar manner to HLA-positive peptide by antigen-specific HLA restricted T cell lines. We obtained a DR1 restricted cell line specific for the haemaglutinin (HA) 307-19AA peptide from R. Lechler, the specificity of which was checked by using DR1-negative and DR1-transfected M1 antigen presenting cells. Unfortunately, several attempts to express gp120 in this and several other cell lines were unsuccessful because of the toxic effect of expressed gp120. The only stable antigen presenting cells expressing gp120 available were obtained from R. Sekaly (Quebec), who successfully transfected gp120 into the Raji B cell line. These cells readily induced fusion of syncytia in CD4 positive cells. These cells were able to induce proliferation of the T cell line HA1.7 only in the presence of the HA peptide 307-19 (Fig. 1).