Key Concepts of Section 23.4

• The MHC, discovered as the genetic region responsible for acceptance or rejection of grafts, encodes many different proteins involved in the immune response. Two of these proteins, class I and class II MHC molecules, are highly polymorphic, occurring in many allelic variations (see Figure 23-21).

• The function of the class I and class II MHC proteins is to bind peptide antigens and display them on the surfaces of cells so that the antigen–MHC protein complex can interact with antigen-specific T-cell receptors on T cells. When an antigen–MHC protein complex on an antigen-presenting cell binds to its complementary T-cell receptor on a T cell, the T cell is activated to assume effector functions, such as the production of cytokines or the ability to kill a virus-infected cell. Class I MHC molecules are found on most nucleated cells, whereas the expression of class II MHC molecules is confined largely to professional APCs such as dendritic cells, macrophages, and B cells.

• The organization and structure of class I and class II MHC molecules is similar and includes a peptide-binding cleft that is specialized for binding a wide variety of peptides (see Figure 23-23).

• Different allelic variants of MHC molecules bind different sets of peptides because the differences that distinguish one allele from another include residues that define the architecture of the peptide-binding cleft (see Figure 23-24). Allelic variation also includes residues in the MHC molecule that directly contact the corresponding T-cell receptor. Thus different allelic variants of an MHC molecule, even if they bind the identical peptide, do not usually react with the same T-cell receptor. This phenomenon is called MHC restriction.

• Class I and class II MHC molecules bind to the peptides in different intracellular compartments: class I molecules bind predominantly to cytosolic materials, whereas class II molecules bind to extracellular materials internalized by phagocytosis, pinocytosis, or receptor-mediated endocytosis.

• The process by which protein antigens are acquired, processed into peptides, and converted into surface-displayed MHC-peptide complexes is referred to as antigen processing and presentation. This process operates continuously in cells that express the relevant MHC molecules, yet can be modulated in the course of an immune response.

• Antigen processing and presentation can be divided into six discrete steps: (1) acquisition of antigen; (2) targeting of the antigen for destruction; (3) proteolysis; (4) encounter of peptides with MHC molecules; (5) binding of peptides to MHC molecules; and (6) display of the peptide-loaded MHC molecules on the cell surface (see Figure 23-27).