It is speculated that a virus-encoded superantigen is involved in the patho
genesis of human and simian immunodeficiency virus infections and that the
accessory protein Nef might be that superantigen. We are able to show, usin
g a murine superantigen screening system, that Nef does nor display feature
s characteristic of a superantigen. Upon transfection into MHC class II exp
ressing antigen-presenting cells, it is expressed, but fails to induce VP-s
pecific expansion of peripheral T lymphocytes, which is a characteristic fe
ature of superantigens in mixed lymphocyte culture. Therefore, we cannot su
pport the hypothesis that Nef is a superantigen. The observations in favor
of that hypothesis must be explained by other mechanisms. (C) 2001 Academic
Press.