Why do αβ T‐cells Need To Recognize Antigen In Such A Complex Way?
Antibodies combat pathogens and their products in the extracellular body fluids where they exist essentially in their native form (Figure 5.30a). Clearly it is to the host’s advantage for the B‐cell receptor to recognize epitopes on the native molecules. αβ T‐cells have quite a different job. In the case of cytotoxic T‐cells they have to seek out and bind to the infected cells and carry out their effector function face to face with the target. The MHC molecules act as markers to tell the effector T‐lymphocyte that it is encountering a cell and the processed peptide acts as a marker of infection (Figure 5.30b). Given that virtually all nucleated cells can become infected with some virus or other, it is necessary for the MHC class I cell marker to be expressed by all nucleated cells in the body because cytotoxic killing requires intimate cell contact between the effector cytotoxic CD8+ αβ T‐cell and the class‐I‐expressing target (infected) cell. In contrast, the secretion of cytokines by helper and regulatory T‐cells does not require cell–cell contact between the effector and the responder cell. Thus the activation of the helper and regulatory T‐cells can be handed over to designated professional APCs that, in addition to expressing MHC class I, also express the MHC class II which is required for presentation of peptides to these CD4+ αβ T‐cells.
Figure 5.30 The fundamental difference between antibody and T‐cell receptor (TCR) recognition of antigen. (a) Antibodies are formed against the native, not denatured, form of infectious agents that are attacked in the extracellular fluids. (b) Effector T‐cells recognize infected cells by two surface markers: the MHC is a signal for the cell, and the foreign peptide is present in the MHC groove as it is derived from the proteins of an intracellular infectious agent. Further microbial cell surface signals can be provided by undegraded antigens and low molecular weight phosphate‐containing antigens (seen by γδ T‐cells), and lipids and glycolipids presented by CD1 molecules.
A comparable situation of enforced cell contact arises when CD1 molecules present processed lipids, glycolipids, and lipoproteins to αβ T‐cells, γδ T‐cells, or NKT cells.