Functional analysis of the env open reading frame in human endogenous retrovirus IDDMK(1,2)22 encoding superantigen activity

Mice harbor a family of endogenous retroviruses, the mouse mammary tumor vi ruses (MMTV), which encode superantigens. These superantigens are responsib le for the deletion of T cells expressing certain V beta chains of the T-ce ll receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II -positive cells, Owing to this and to the similarity of the human and murin e immune systems, it was speculated that human endogenous retroviruses migh t also code for superantigens. Recently, it was reported that a proviral cl one (IDDMK(1,2)22) of the human endogenous retrovirus family HTDV/HERV-K en codes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) w hich were identical or very similar to IDDMK(1,2)22. When we transfected th ese vectors into A20 cells, a murine B-cell lymphoma, we were able to demon strate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a V beta-speci fic fashion, the most prominent feature of superantigens.