Determinants on Major Histocompatibility Complex Class I Molecules Recognized by Cytotoxic T Lymphocytes

The antigen specificity of cytotoxic T lymphocytes (CTL) cells is a result of the recognition of class I molecules on target cells that are encoded by genes in the major histocompatibility complex (MHC). These molecules consist of a 40,000–45,000 Da heavy chain noncovalently bound to a 12,000 Da light chain, β₂-microgIobulin (β₂-M). Although class I molecules expressed by an individual are invariant, the alleles of each gene that encode class I molecules are highly polymorphic such that most species possess a large number of antigenically diverse class I alloantigens. The polymorphism found in class I molecules is not randomly distributed, but rather localized to the α₁ and α₂ domains. In contrast to the class I heavy chain, β₂-M is invariant within a species, although in the mouse limited polymorphism has been detected. Although class I molecules within a species are ∼80–90% homologous, the fact that T cells readily distinguish among class I alloantigens indicates that the immune system focuses on the polymorphic features of these molecules. To accomplish this, CTL utilize α and β chains of their T cell receptor to recognize antigen in the context of class I molecules. This chapter examines the various approaches used to characterize determinants on class I molecules that are recognized by both alloreactive and antigen-specific class I-restricted CTL. Studies attempting to examine the nature of the determinants recognized by CTL have taken advantage of the variants of normal class I molecules. The role of carbohydrates and β₂-M in controlling epitopes recognized by CTL are discussed in the chapter.