Two Types of Antigens Animals are confronted with numerous substances and organisms that threaten their existence. These may be present in extracellular body fluids (eg, toxins, bacteria) or harbored in the animals’ own cells (eg, viruses, oncogene products). This distinction is critically important to thymus-derived lymphocytes (T cells), which constitute an essential component of immune responses to many agents. T cells have evolved parallel systems for recognizing intracellular and extracellular antigens. In both systems, antigens are recognized only when bound to molecules of the major histocompatibility complex (MHC). Two Antigen Binding Molecules The MHC encodes two types of cell surface molecules that act as receptors for protein antigens. Class I molecules consist of a highly polymorphic integral membrane glycoprotein a chain noncovalently bound to f3z-microglobulin. Class II molecules consist of two noncovalently bound, highly polymorphic, integral membrane glycoproteins. As with other cell surface proteins, MHC molecules are cotranslationally inserted into the endoplasmic reticulum (ER) and, following chain assembly, are transported to the plasma membrane via the Golgi complex and post-Golgi complex vesicles.

Crystallographic analysis of the structure of class I molecules reveals a groove at the top surface of the molecule formed by the two amino-terminal domains (Bjorkman et al., 1987). Functional studies strongly implicate the groove in antigen binding, and in the crystal structure the groove is indeed occupied by a ligand. Although the three-dimensional structure of the class II molecule is not yet available, a similar antigen binding site can be modeled by aligning structural elements conserved between class I and II molecules (Brown et al., 1988). Two T Cells