Immune-response gene-associated antigens (Ia/DR). Structure and function in immunologically related diseases

Major histocompatibility complex-determined antigens were originally identified as a consequence of their ability to induce rejection of tissue grafts between organisms that are not genetically identical. Currently, much is known about their biochemical nature and intended biologic functions. Major histocompatibility complex antigens are found on three types of glycoprotein molecules. One type (class I) is associated with β₂-microglobulin in the cell-surface membranes of all body tissues and includes H-2K and D molecules in mice and HLA-A, B, and C molecules in humans. These antigens are the major cause of rejection of transplanted organs. The other two types of glycoproteins (class II) are noncovalently linked to each other, are found in the cell-surface membranes of a limited number of cell types, and include H-2-Ia molecules in mice and HLA-DR molecules in humans. They are noted for their ability to elicit graft-versus-host disease. Both class I and class II molecules are, however, important for the immune recognition of pathogens, although the types of responses they modulate are different. Class I molecules are important in the recognition of cell-surface antigens, whereas class II molecules control responsiveness to soluble antigens. Major histocompatibility complex-encoded molecules are also involved in certain autoimmune diseases. As our understanding of major histocompatibility complex-controlled immune responsiveness broadens and hybridoma and gene-cloning technology advances, specific enhancement of desired immune responses and suppression of deleterious ones will most likely become possible.