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.
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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.
