Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

T CELLS AND MHC PROTEINS
1327
receptor for
co-stimulatory
protein
TCR
foreign peptide
(antigen)
MHC
protein
Figure 24–34 The three general types of
proteins on the surface of an activated
dendritic cell involved in activating a
T cell. Although only membrane-bound
co-stimulatory molecules are shown,
activated dendritic cells also secrete
soluble co-stimulatory molecules. The
invariant polypeptide chains that are
always stably associated with the
TCR are not shown; they are illustrated
in Figure 24–45B and Movie 24.7.
cell–cell
adhesion
proteins
co-stimulatory
protein
T CELL
ACTIVATED
DENDRITIC CELL
Both class I and class II MHC proteins are heterodimers, in which two extracellular
domains form a peptide-binding groove, which always has a variable small
peptide bound in it. In class I MHC proteins, the two domains that form the peptide-binding
groove are provided by the transmembrane α chain, which is noncovalently
associated with a small subunit called β 2 ‐microglobulin; in class II MHC
proteins, a different α chain and a large noncovalently associated β chain each
contribute an extracellular domain to form the peptide-binding groove (Figure
MBoC6 m25.45/24.36
24–36). A TCR binds to both the peptide and the ridges of the binding groove.
Humans have three major class I proteins, called HLA‐A, HLA‐B, and HLA‐C,
and three class II proteins, called HLA‐DR, HLA‐DP, and HLA‐DQ (HLA stands
for human-leukocyte-associated, as these proteins were first demonstrated on
human leukocytes). Figure 24–37 shows how the genes that encode these proteins
are arranged on human chromosome 6.
There are important differences between the class I and class II MHC proteins
with regard to the cell types that express them and the origin of the peptides
in their peptide-binding grooves. Almost all of our nucleated cells express
class I proteins. Their peptide-binding groove displays one of a diverse collection
of peptides (typically 8–10 amino acids in length). In a healthy cell, the peptides
originate from the cell’s own cytosolic and nuclear proteins that have undergone
partial degradation in proteasomes in the processes of normal protein turnover
and quality control mechanisms. Some of the peptide fragments produced in this
way are actively transported into the lumen of the endoplasmic reticulum (ER),
through a specialized transporter in the ER membrane, where they are loaded
onto newly synthesized class I MHC α chains; once a peptide binds, the α chain
can assemble with its partner chain. The resulting self-peptide–MHC complex is
then transported through the Golgi apparatus to the cell surface. Such complexes
are not dangerous, however, because the cytotoxic T cells that could recognize
class I
MHC
protein
CYTOTOXIC T CELL
T C
TCR
fragment
of foreign
protein
dendritic cell
or target cell
HELPER OR REGULATORY T CELL
class II
MHC
protein
T H
TCR
fragment
of foreign
protein
Figure 24–35 Recognition by T cells
of foreign peptides bound to MHC
proteins. Cytotoxic T cells recognize
foreign peptides in association with class
I MHC proteins, whereas helper T cells
and regulatory T cells recognize foreign
peptides in association with class II
MHC proteins. In both cases, the T cell
recognizes the peptide–MHC complexes
on the surface of an APC—either a
dendritic cell or a target cell. Some
regulatory T cells recognize self peptides
in association with class II MHC proteins
(not shown).