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

1328 Chapter 24: The Innate and Adaptive Immune Systems
peptide bound in
peptide-binding groove
peptide bound in
peptide-binding groove
peptide in
peptide-binding
groove
α 1
α 2
α 1
β 1
S
S
S
S
NH 2
NH 2
H 2 N
NH 2
β 2 -
microglobulin
S
S
HOOC
S
S
α 3
Ig-like
domain
EXTRACELLULAR
SPACE
S S
α 2 S S β 2
plasma
membrane
NH 2
α chain
CYTOSOL
COOH
COOH
COOH
COOH
α chain
β chain
(A) CLASS I MHC PROTEIN
(B) CLASS II MHC PROTEIN
(C)
TOP VIEW OF BINDING
GROOVE OF CLASS I
MHC PROTEIN
Figure 24–36 Class I and class II MHC proteins. (A) The α chain of the class I molecule has three extracellular domains, α 1 , α 2 , and
α 3 , each encoded by a separate exon. The α chain is noncovalently associated with a smaller polypeptide chain, β 2 ‐microglobulin,
which is not encoded within the MHC region of the genome. The α 3 domain and β 2 ‐microglobulin are Ig‐like. While β 2 ‐microglobulin is
invariant, the α chain is extremely polymorphic, mainly in the α 1 and α 2 domains. (B) In class II MHC proteins, both the α chain and the
β chain are encoded within the MHC and are polymorphic, mainly in the α 1 and β 1 domains; the α 2 and β 2 domains are Ig‐like. Thus,
there are striking similarities between class I and class II MHC proteins. In both, the two outermost domains (shaded in blue) are
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polymorphic and interact to form a groove that binds peptide fragments. (C) The three-dimensional structure of the peptide-binding
groove of a human class I MHC protein is viewed from above, with bound peptide shown schematically; a peptide must be bound in the
groove for the MHC protein to assemble and be transported to the cell surface. The sides of the groove are formed by two α helices,
and the floor is formed by a β pleated sheet. The S–S disulfide bond is shown in red (Movie 24.8 and Movie 24.9). (C, adapted from
P.J. Bjorkman et al., Nature 329:506–512, 1987. With permission from Macmillan Publishers Ltd.)
them have been either eliminated or inactivated, or suppressed by regulatory T
cells in the process of self-tolerance. By contrast, in a cell infected by a pathogen
such as a virus, the pathogen proteins will be processed in the same way, and
peptides derived from them will be displayed on the infected cell surface bound
to class I MHC proteins; there, they are recognized by cytotoxic T cells expressing
the appropriate TCRs, thereby targeting the infected cell for destruction (Figure
24–38).
In general, only antigen-presenting cells (APCs) express class II MHC proteins.
Dendritic cells are referred to as professional APCs, as they are specialized
for this function and only they can activate naïve T cells. Other immune cells that
are targets of effector T cell regulation, including B cells and macrophages, are
nonprofessional APCs. All APCs load their newly synthesized class II MHC proteins
with peptides derived mainly from extracellular proteins that are endocytosed
and delivered to endosomes. The newly synthesized class II MHC proteins
initially contain an invariant chain, which occupies the peptide-binding groove
human
chromosome 6
class II MHC genes
HLA-DP HLA-DQ HLA-DR
β α β α β β α
HLA complex
class I MHC genes
HLA-B HLA-C HLA-A
Figure 24–37 Human MHC genes. This
simplified schematic drawing shows the
location of the genes that encode the
transmembrane subunits of class I (light
green) and class II (dark green) MHC
proteins. The genes shown encode three
types of class I MHC proteins (HLA‐A,
HLA‐B, and HLA‐C) and three types of
class II MHC proteins (HLA‐DP, HLA‐DQ,
and HLA‐DR). An individual can therefore
make six types of class I MHC proteins
(three encoded by maternal genes and
three by paternal genes) and more than six
types of class II MHC proteins. Because
of the extreme polymorphism of the MHC
genes, the chances are very low that
the maternal and paternal alleles will be
the same. The number of class II MHC
proteins that can be made is greater than
six because there are two DR β genes
and because maternally encoded and
paternally encoded polypeptide chains can
sometimes pair. The entire region shown
spans about seven million base pairs and
contains other genes that are not shown.