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

1330 Chapter 24: The Innate and Adaptive Immune Systems
HELPER T CELL
plasma
membrane
antigenic peptide
folded protein antigen
RECOGNITION BY
HELPER T CELL
CYTOSOL
early
endosome
late
endosome
ENDOCYTOSIS AND
DELIVERY TO ENDOSOME
fragment of
invariant chain
DENDRITIC OR
TARGET CELL
DELIVERY OF PEPTIDE–
MHC COMPLEX TO
PLASMA MEMBRANE
FOR RECOGNITION
BY HELPER T CELL
LIMITED PROTEOLYSIS OF
ANTIGEN AND INVARIANT
CHAIN LEAVES FRAGMENT
OF INVARIANT CHAIN IN
BINDING GROOVE
OF MHC PROTEIN
RELEASE OF
INVARIANT CHAIN
FRAGMENT AND
BINDING OF
ANTIGEN-DERIVED
PEPTIDE
class II
MHC
protein
INVARIANT CHAIN
DIRECTS CLASS II
MHC PROTEIN TO
LATE ENDOSOME
invariant chain
Golgi
apparatus
trans Golgi
network
Figure 24–39 The processing of an extracellular protein antigen for presentation to
a helper T cell. This simplified depiction shows how peptide–class-II-MHC complexes
are formed in endosomes and delivered via vesicles to the cell surface. Viral envelope
glycoproteins can also be processed by this pathway for presentation to helper T cells
(not shown): these glycoproteins are normally made in the ER and transported via the
Golgi for insertion into the plasma membrane; although most of these glycoproteins will
be incorporated into the envelope of budding viral particles, some will be endocytosed
and enter endosomes, from where they can enter the class II MHC processing pathway.
During an infection, only a small fraction of the many thousands of MHC proteins
on the surface of an APC or target cell will have pathogen peptides bound
to them. This is sufficient, however: fewer than 50 copies of such a peptide–MHC
complex on a dendritic cell, for example, can activate a helper T cell that has a
TCR that binds the complex with a high-enough affinity. Table 24–3 compares the
properties of class I and class II MHC proteins.
MBoC6 m25.61/24.41
MHC Proteins Are the Most Polymorphic Human Proteins Known
Although any individual can make only a small number of different class I and class
II MHC proteins, together, these proteins must be able to present peptide fragments
from almost any foreign protein to T cells. Thus, unlike the antigen-binding
site of an Ig protein, the peptide-binding groove of each MHC protein must be
Table 24–3 Properties of Human Class I and Class II MHC Proteins
Class I
Class II
Genetic loci HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ, HLA-DR
Chain structure α chain +
β 2 -microglobulin
α chain + β chain
Cell distribution Most nucleated cells Dendritic cells, B cells,
macrophages, thymus epithelial
cells, some others
Presents antigen to Cytotoxic T cells Helper T cells, regulatory T cells
Source of peptide
fragments
Mainly proteins made
in cytoplasm
Mainly endocytosed plasma
membrane and extracellular
proteins
Polymorphic domains α 1 + α 2 α 1 + β 1
Recognition by
co-receptor
CD8
CD4