Functional Implications of the Structural Diversity of Murine Ia and Human DR Antigens

Abstract

The survival of an organism depends on the ability of its cells to recognize each other and their immediate environment. The immune responses found in most vertebrates are prime instances of vitally important interactions among subpopulations of cells. In the sophisticated immune system of mammals, the generation of immune responses requires interactions among T cells, B cells, and macrophages. The I and HLA-D regions of the murine and human major histocompatibility complexes (MHC) contain genes that regulate these cell interactions. This role for these genes was recognized with the observation that subpopulations of immune cells from individuals possessing different forms (haplotypes) of the MHC failed to interact. The cellular interactions genetically regulated by the MHC are apparently mediated by cell-surface glycoproteins known as Ia antigens in mice and HLA-DR antigens in humans. These molecules display a high degree of serological and structural polymorphism, a consequence of the high degree of polymorphism of the MHC. The genetic restrictions placed on cellular interactions by the MHC presumably reflect the requirement for recognition of haplotype-specific Ia or HLA-DR antigens. Consequently, molecular analysis of the structural diversity of Ia and HLA-DR antigens provides a basis for understanding how cells recognize and communicate with each other.