Effects of HIV-1 peptides on T-cell receptor variable beta chain families

Superantigens (SAGs) selectively stimulate expansion and then deletion of specific T cell antigen receptor (TCR) variable beta chain (Vbeta) families. We investigated six synthetically produced HIV-1-related peptides for evidence of SAG activity: three derived all or in part from the transmembrane gp41 protein and three from the genetic sequence of the tRNA binding region. The first three were chosen because they are highly immunogenic; the second three, because their genetic sequence is completely homologous to a region of the mouse mammary tumor virus, a known superantigen. We cultured peripheral blood mononuclear cells (PBMC) of HIV-negative, healthy human donors with each of these six HIV-1 peptides. Resting and blastic CD4(+) and CD8(+) lymphocytes were assessed pre- and post-culture using 3-color cytofluorometry and monoclonal antibodies to CD4, CD8, and 14 human TCR Vbeta families. Significance testing was done using a Student t-test. Two of the HIV-1 peptides showed possible SAG activity, one from gp41 transmembrane protein, and one from tRNA binding region. Peptide JJ1, from gp41, was associated with an increased percentage of resting and blastic Vbeta 5, 8, and 21 in CD4(+), but not CD8(+) lymphocytes (3/3 donors, p = 0.014, p = 0.011, and p = 0.019, respectively, for blastic CD4(+) lymphocytes). Peptide JJ5, from the tRNA binding region, was associated with an increased percentage of resting and blastic Vbeta 5, 12, 16, and 17 in CD8(+) but not CD4(+) lymphocytes (4/4 donors for blastic CD8(+) lymphocytes, 3/4 for resting CD8(+) lymphocytes, p < 0.05 for each Vbeta family, for blastic CD8(+) lymphocytes). These results suggest that peptide JJ1 may have SAG activity restricted to CD4(+) lymphocytes and that peptide JJ5 may have restricted cytotoxic activity, associated with CD8(+) cell responsiveness. For both, the activities would lead to increased localized cytokine production and work to the advantage of the virus. These antigens might thus represent potential targets for future antiretroviral therapy.