Genes of the Major Histocompatibility Complex of the Mouse

In the past 2 years our understanding of the major histocompatibility complex has advanced dramatically because of the rapid progress made by molecular genetics. Biologists can now begin to dissect the molecular nature of one of the most fundamental problems in eukaryotic biology-the ability of organisms to discriminate between self and nonself. Even the most primi­ tive of metazoa, the sponges, exhibit cell-surface recognition systems capa­ ble of identifying and destroying nonself, presumably to preserve the integrity of individuals growing in densely populated environments (34). For example, when two genetically identical sponges are apposed, the indi­ viduals fuse to form a single organism. However, when two genetically dissimilar sponges are joined, there is a reaction leading to tissue destruction at the boundary between the two individuals (35, 36). Presumably, cell­ surface structures recognize nonself and trigger effector mechanisms that lead to the destruction of the foreign tissue. Perhaps the most striking feature of the molecules involved in these cell-surface recognition phenom­ ena is their enormous diversity or polymorphism. More than 900 genetically distinct sponges have the capacity to reject one another after apposition (35). Self/nonself recognition systems in other invertebrates and vertebrates appear to display similar characteristics. Thus, three features are fundamen­ tal to self/nonself recognition systems-cell-surface recognition structures, effector mechanisms that lead to the destruction of nonself, and a high degree of polymorphism in the recognition structures. Mammals have self/nonself recognition systems encoded by a chromoso­ mal region termed the major histocompatibility complex (MHC) with pre-