The Keys to Cell-Mediated Immunity

THE HUMAN immunodeficiency virus (HIV) pandemic has made us aware of the intimate relationships between viruses and the immune system. These human lentiviruses grow in lymphocytes of the CD4+ subset and are probably controlled, at least for a time, by the CD8+ effectors of cell-mediated immunity (CMI). When we discuss CMI-based strategies to limit HIV infection, the debate is framed by the efforts made over the past 20 years to understand the way that the major histocompatibility complex (MHC) glycoproteins function in viral immunity. This article places these efforts in historical context and, together with the accompanying article by Rolf Zinkernagel,¹relates how our understanding of virus-specific CMI and the biological role of the MHC became intertwined. BACKGROUND In the early 1970s, the international effort on virus-specific CMI was minuscule. Most virologists had shifted their attention from whole-animal studies, in which virology and immunology approaches were inextricably linked, to