Functional evaluation of HIV/SIV Nef as superantigen

It is speculated that a virus-encoded superantigen is involved in the pathogenesis of human and simian immunodeficiency virus infections and that the accessory protein Nef might be that superantigen. We are able to show, using a murine superantigen screening system, that Nef does not display features characteristic of a superantigen. Upon transfection into MHC class II expressing antigen-presenting cells, it is expressed, but fails to induce Vbeta-specific expansion of peripheral T lymphocytes, which is a characteristic feature of superantigens in mixed lymphocyte culture. Therefore, we cannot support the hypothesis that Nef is a superantigen. The observations in favor of that hypothesis must be explained by other mechanisms.