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
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and prevents it from prematurely binding a peptide until the class II MHC protein
reaches specialized vesicles, which fuse with endosomes. Here, the invariant
chain is removed and peptide fragments (typically 12–20 amino acids long)
produced from endocytosed proteins can bind to the groove of the class II MHC
proteins, which are then transported to the plasma membrane for display on the
surface of the APC. In a healthy host cell, class II MHC protein grooves are loaded
with self-peptides derived from normal proteins and will be ignored by T cells
because of self-tolerance mechanisms. During an infection, however, pathogen
proteins are also endocytosed and processed in the same way, enabling APCs to
present pathogen peptides bound to class II MHC proteins to T cells expressing an
appropriate TCR (Figure 24–39).
The distinction just discussed between the antigen-processing pathways for
loading peptides onto class I and class II MHC proteins is not absolute. Dendritic
cells, for example, need to be able to activate cytotoxic T cells to kill virus-infected
cells even when the virus does not infect dendritic cells themselves. To
do so, specialized subsets of dendritic cells use a process called cross-presentation,
which begins when these noninfected dendritic cells phagocytose virus-infected
host cells or their fragments. The ingested viral proteins are then released
by an unknown mechanism from phagolysosomes into the cytosol, where they
are degraded in proteasomes; the resulting protein fragments are then transported
into the ER lumen, where they load onto assembling class I MHC proteins.
Cross-presentation in dendritic cells is not confined to endocytosed pathogens
and their products: it also operates to activate cytotoxic T cells against tumor antigens
of cancer cells and the MHC proteins of foreign organ grafts.
cytotoxic T cell
viral RNA
viral envelope
CYTOSOL
endosome
VIRUS INFECTION
endosome
REPLICATION AND
TRANSLATION OF
VIRAL RNA
internal viral
protein
ENDOCYTOSIS AND
DELIVERY TO ENDOSOME
RNA
plasma
membrane
FUSION OF VIRUS WITH ENDOSOME
MEMBRANE AND ESCAPE OF VIRAL
RNA AND PROTEIN INTO CYTOSOL
internal
viral protein
assembled class I
MHC protein with
bound viral
peptide
ER
ABC transporter
class I MHC α chain
RECOGNITION OF VIRAL
PEPTIDE BY CYTOTOXIC T CELL
TRANSPORT OF PEPTIDE–MHC
COMPLEX THROUGH GOLGI
APPARATUS TO CELL SURFACE
Golgi apparatus
BINDING OF PEPTIDE TO
α CHAIN STABILIZES ASSEMBLY OF
α CHAIN WITH β 2 -MICROGLOBULIN;
PEPTIDE–MHC COMPLEX IS THEN
TRANSPORTED TO THE GOLGI
APPARATUS
β 2 -microglobulin
dendritic or target cell
PROTEOLYSIS OF
SOME VIRAL PROTEIN
MOLECULES BY
PROTEASOMES
proteasome
viral
peptides
ACTIVE TRANSPORT
OF PEPTIDES INTO
ER LUMEN
Figure 24–38 The processing of an extracellular foreign protein for presentation to cytotoxic T cells. An effector cytotoxic T cell kills a virusinfected
cell when it recognizes fragments of an internal viral protein bound to class I MHC proteins on the surface of the infected cell. Not all viruses
enter the cell in the way that this enveloped RNA virus does, but fragments of internal viral proteins always follow the pathway shown. Only a small
proportion of the viral proteins synthesized in the cytosol are degraded and transported to the cell surface, but this is sufficient to attract an attack
by a cytotoxic T cell. Several chaperone proteins in the ER lumen aid the folding and assembly of class I MHC proteins (not shown). The assembly
of class I MHC proteins and their transport to the cell surface require the binding of either a self or foreign peptide (Movie 24.10).