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

Superantigens (SAGs) selectively stimulate expansion and then deletion of s pecific T cell antigen receptor (TCR) variable beta chain (VP) families. We investigated six synthetically produced HIV-l-related peptides for evidenc e 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. Th e first three were chosen because they are highly immunogenic; the second t hree, because their genetic sequence is completely homologous to a region o f the mouse mammary tumor virus, a known superantigen. We cultured peripher al blood mononuclear cells (PBMC) of HIV-negative, healthy human donors wit h each of these six HIV-1 peptides. Resting and blastic CD4(+) and CD8(+) l ymphocytes were assessed pre- and post-culture using 3-color cytofluorometr y and monoclonal antibodies to CD4, CD8, and 14 human TCR VP families. Sign ificance 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 i ncreased percentage of resting and blastic V beta 5, 8, and 21 in CD4(+), b ut 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 b inding region, was associated with an increased percentage of resting and b lastic V beta 5, 12, 16, and 17 in CD8(+) bur nor CD4(+) lymphocytes (4/4 d onors for blastic CD8(+) lymphocytes, 3/4 for resting CD8(+) lymphocytes,p < 0.05 for each V<beta> family, for blastic CD8(+) lymphocytes). These resu lts suggest that peptide JJ1 may have SAG activity restricted to CD4(+) lym phocytes and that peptide JJ5 may have restricted cytotoxic activity, assoc iated 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 an tiretroviral therapy. (C) American Society for Histocompatibility and Immun ogenetics, 2000. Published by Elsevier Science Inc.