Abstract: Novel recombinant polypeptides are disclosed herein that include a CD4 polypeptide ligated at its C-terminus with a portion of an immunoglobulin comprising a hinge region and a constant domain of a mammalian immunoglobulin heavy chain. The portion of the IgG is fused at its C-terminus with a polypeptide comprising a tailpiece from the C-terminus of the heavy chain of an IgA antibody or a tailpiece from a C-terminus of the heavy chain of an IgM antibody. Also disclosed herein are methods for using these CD4-fusion proteins.