Research as early as the 1960s on the nature of T-cell antigen recognition showed that the physicochemical forms of antigens that are recognized by T cells are different from those recognized by B lymphocytes and antibodies. This knowledge led to the discovery of how antigens are seen by T cells. Several features of antigen recognition are unique to T lymphocytes (Table1).
Table1. Features of Major Histocompatibility Complex–Dependent Antigen Recognition by T Lymphocytes
Most T lymphocytes recognize only short peptides. The rea son for this is that MHC molecules can bind and display only peptides and can accommodate peptides of limited length. As a result, T cell–mediated immune responses are usually induced by protein antigens (the natural source of peptides), whereas humoral immune responses are induced by protein and nonprotein antigens. Some T cells are specific for small chemical sub stances (not peptides) such as urushiol of poison ivy, β-lactams of penicillin antibiotics, and even metal ions such as nickel and beryllium. In these situations, the chemicals bind to self proteins, including MHC molecules, and the T cells recognize the modified self peptides or altered MHC molecules. The pep tide specificity of T cells is true for CD4+ and CD8+ cells, there are some other small populations of T cells that are capable of recognizing nonprotein antigens. In striking contrast to T cells, B cells can recognize many more types of antigens, including intact proteins, peptides, nucleic acids, carbohydrates, lipids, and small chemicals.
The antigen receptors of CD4+ and CD8+ T cells are specific for peptide antigens that are displayed by MHC molecules (Fig. 1). The only known function of MHC molecules is to bind and display peptides for recognition by CD4+ and CD8+ T cells. MHC molecules are highly polymorphic, meaning that there are many alleles in the population and each individual inherits and expresses only a small fraction of these alleles. Each MHC molecule can present many but not all peptides, and each T cell can recognize only one or a few peptides displayed by one MHC molecule. MHC recognition is also required for the maturation of these T cells, ensuring that mature T cells in each individual are restricted to recognizing only MHC molecules of that individual with bound anti gens. This phenomenon is called MHC restriction. There are two classes of MHC molecules, called class I and class II. CD4+ T cells recognize peptides displayed by MHC class II (MHC-II), and CD8+ T cells recognize peptides displayed by MHC class I (MHC-I).
Fig1. A model for T-cell recognition of a peptide-major histocompatibility complex (MHC). This illustration shows an MHC molecule binding and displaying a peptide and a T-cell receptor recognizing the complex of peptide and MHC molecule. As discussed later in the text, MHC-associated peptides contain some residues that anchor them into pockets in the cleft of the MHC molecule and other residues that are recognized by T-cell antigen receptors. MHC residues that may vary among individuals (polymorphic residues) are also recognized by the T-cell receptor. Thus, T cells simultaneously see both peptide antigens and the MHC molecules that present the antigens.
