Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

5.1 The Major Histocompatibility Complex (MHC) Antigen-Processing and -Presentation Pathways
Fig. 5.2 The MHC class I
APM. Ubiquitinylated proteins
are cleaved into peptides by the
multicatalytic proteasome subunits
which are then transported
via the TAP heterocomplex
into the ER. In the ER, peptides
assemble with the MHC
class I HC and b2-m to form the
trimeric MHC class I complex,
which is then transported
through the Golgi complex to
the cell surface for presentation
to CD8 + cytotoxic T cells (A).
The MHC class I/peptide assembly
is assisted by various
chaperones, such as calnexin,
calreticulin, ERp57 and tapasin,
which partially form the multimeric
TAP complex (B).
(see color plates page XIX)
selection and stabilization of the MHC class I-loading complex [8]. In addition, other
ER-resident cofactors, such as the chaperones calnexin and calreticulin, and the thiol
oxidoreductase ERp57, stabilize the MHC class Imolecules during their folding
and/or assembly. Moreover, they are also partially involved at different stages in the
formation of the multisubunit loading complex [9±11]. Peptide binding induces the
dissociation of the peptide/MHC class IHC/b2-m trimer which is then transported
via the trans-Golgi apparatus to the cell surface for presentation to CD8 + cytotoxic T
lymphocytes (CTLs).
5.1.2
The MHC Class II APM
The MHC class II antigen-processing pathway is even more complex than the MHC
class I APM. It allows the formation and delivery of peptide/MHC class II complexes
to the cell surface, where they are presented to CD4 + T cells (Fig. 5.3) [12, 13]. In contrast
to MHC class Imolecules, MHC class IImolecules present peptides that are
mainly derived from exogenous antigens internalized into the endocytic pathway.
The newly synthesized heterodimeric MHC class II molecules consisting of the a
and b chains associate in the ER with the invariant chains (Ii) that inhibit peptide
binding to MHC class II molecules while they are in the ER. They form a nonameric
complex which is then targeted to specialized MHC class II compartments of the en-
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