Use of human CD4 transgenic mice for studying immunogenicity of HIV-1 envelope protein gp120

HIV-1 envelope protein, gp120, is a major immunogenic protein of the AIDS v irus. A specific feature of this protein is its interaction with the recept or protein, human CD4, an important component of the immune system. This in teraction might affect the immunogenic properties of the gp120 and modulate the immune response towards HIV. To test this hypothesis we used human CD4 -transgenic mice for immunization with gp120. The dynamics of the immune re sponse towards gp120, CD4 and other proteins was followed. The results show that the primary immune response to gp120 (two weeks) developed somewhat f aster in CD4-transgenic mice versus non-transgenic mice. Both animals, howe ver, ultimately mounted the same level of response over time. The primary i mmune response to gp120 when complexed with soluble CD4 before the immuniza tion, developed similarly in both groups. The secondary immune response was earlier and markedly stronger in non-transgenic mice compared with the tra nsgenic mice where a less efficient memory response to gp120 was observed. The ability of gp120 to directly interact with CD4+ helper lymphocytes appe ars to affect the humoral response towards this antigen. Moreover, these ef fects illustrate how viral modulation of these cells may in turn lead to po tentially different states of immunological equilibrium.