Chapter 6 Flashcards
T cells recognize antigens only in the form of what?
peptides displayed by the products of self MHC genes
on the surface of APCs
CD4+
helper T lymphocytes recognize antigens in association with what?
class II MHC gene products (class II MHC–restricted recognition)
CD8+
CTLs recognize antigens in
association with what?
class I gene products (class I MHC–restricted recognition)
Specialized APCs, such as dendritic cells, macrophages, and B lymphocytes do what?
capture extracellular
protein antigens, internalize and process them,
and display class II–associated peptides to CD4+
T
cells
Dendritic cells are the most efficient APCs for what?
initiation of primary responses by activating naive
T cells, and macrophages and B lymphocytes
present antigens to differentiated helper T cells in the effector phase of cell-mediated immunity and
in humoral immune responses, respectively
All
nucleated cells can present what?
class I–associated peptides, derived from cytosolic proteins such as viral
and tumor antigens, to CD8+
T cells
what is the MHC?
a large genetic region coding for class I and class II MHC molecules as well as for other proteins. MHC genes are highly polymorphic
Class
I MHC molecules are composed of what?
an α (or heavy)
chain in a noncovalent complex with a nonpolymorphic polypeptide called β2-microglobulin
The class II molecules contain what?
n two MHC-encoded polymorphic chains, an α chain and a β chain
Both
classes of MHC molecules consist of what?
an extracellular peptide-binding cleft, a nonpolymorphic Ig-like
region, a transmembrane region, and a cytoplasmic
region
The Ig-like domains of class I and class II molecules contain the binding sites for what?
the T cell
coreceptors CD8 and CD4, respectively
The function of MHC-encoded class I and class II molecules is to what?
bind peptide antigens and display
them for recognition by antigen-specific T lymphocytes
What is the difference between peptide antigens associated with class 1 and 2 molecules?
Peptide antigens associated with class I molecules are recognized by CD8+ T cells, whereas class II–associated peptide antigens are recognized by CD4+ T cells
Every MHC molecule has a broad
specificity for what?
peptides and can bind multiple peptides that have common structural features, such
as anchor residues
Some
polymorphic MHC residues determine what?
the binding
specificities for peptides by forming structures,
called pockets, that interact with complementary
residues of the bound peptide, called anchor residues
What is the difference in expression of Class 1 and 2 molecules?
Class I molecules are expressed on all nucleated
cells, whereas class II molecules are expressed
mainly on specialized APCs, such as dendritic cells,
macrophages, and B lymphocytes, and a few other
cell types, including endothelial cells and thymic
epithelial cells
The expression of MHC gene products is enhanced by what?
inflammatory and immune
stimuli, particularly cytokines like IFN-γ, which
stimulate the transcription of MHC genes
what is antigen processing?
the conversion of native proteins into MHC-associated peptides. This process
consists of the introduction of exogenous protein
antigens into vesicles of APCs or the synthesis of
antigens in the cytosol, the proteolytic degradation
of these proteins into peptides, the binding of peptides to MHC molecules, and the display of the
peptide-MHC complexes on the APC surface for
recognition by T cells
what happens with class 1 associated antigen presentation?
cytosolic proteins are proteolytically degraded in the
proteasome, generating peptides with features that
enable them to bind to class I molecules. These
peptides are delivered from the cytoplasm to the
ER by an ATP-dependent transporter called TAP
Newly synthesized class I MHC–β2-microglobulin dimers in the ER are associated with what?
the TAP
complex and receive peptides transported into the
ER. Stable complexes of class I MHC molecules
with bound peptides move out of the ER, through
the Golgi complex, to the cell surface
what happens in class II associated antigen presentation?
extracellular proteins are internalized into endosomes,
where these proteins are proteolytically cleaved by
enzymes that function at acidic pH. Newly synthesized class II MHC molecules associated with the Ii
are transported from the ER to the endosomal
vesicles. Here the Ii is proteolytically cleaved, and
a small peptide remnant of the Ii, called CLIP, is
removed from the peptide-binding cleft of the
MHC molecule by the DM molecules
These pathways of MHC-restricted antigen presentation ensure what?
that most of the body’s cells are
screened for the possible presence of foreign antigens. The pathways also ensure that proteins from
extracellular microbes preferentially generate peptides bound to class II MHC molecules for recognition by CD4+
helper T cells, which activate effector
mechanisms that eliminate extracellular antigens.
Conversely, proteins synthesized by intracellular
(cytosolic) microbes generate peptides bound to
class I MHC molecules for recognition by CD8+
CTLs, which function to eliminate cells harboring
intracellular infections.
immunogenicity of
foreign protein antigens depends onwhat?
the ability of
antigen-processing pathways to generate peptides
from these proteins that bind to self MHC
molecules.
