The concept of major histocompatibility complex (MHC) proposed by Gorer in 1937 (1) has been intensively developped in the last twenty years. Denoted H-2 in mice and HLA (Human Lymphocyte Locus A) in humans, it is a well defined locus on chromosome 17 in mice and on the short arm of chromosome 6 in humans. This system and its functions are present in all vertebrates (2). Following the physicochemical characteristics of proteins expressed by these genes, 3 families of MHC products have been defined and denoted class I, II and III (3). The first part of this chapter attempts to describe the main concepts associated with class I and II MHC antigens, especially their specific biological functions. We do not attempt to present class III products which correspond to proteins implicated in the complement system and do not seem to play a major role in the immune response directed against cancer.