MHC and Antigen Presentation to T cells Flashcards
T cell receptor (TCR) is composed of 2 polypeptide chains ____ and ____
which are made up of ____ and ____ regions
alpha and beta
constant and variable
the genes coding for TCR, CD3, CD4, CD8, and MHC are members of the ____ super family
Ig
unlike Abs, TCRs do not recognize native antigen, but can only bind processed Ag presented in associated with ____ molecules
MHC
unlike BCR (Abs), TCR are never produced in a ______ form
secreted
the ____ region of alpha and beta chains of TCR constitute the Ag-binding site
variable
some unconventional T cells express a TCR consisting of ____ and ____ chains
gamma and delta
gamma/delta T cells have a broader specificity for unconventional Ag such as ____ and ____
(don’t need APCs for activation)
HSPs and phospholipids
TCR is associated with nearby ___ signaling complexes
CD3
composed of gamma, delta, and epsilon chains
____ Ags are presented to T cells in association with MHC molecules
peptide
class I MHC is expressed on all
nucleated cells
class II is expressed on
professional Ag-presenting cells (DCs, mast cells, B cells)
in class I MHC, what chain(s) contributes to peptide binding groove
only alpha chain
in class II MHC, what chain(s) contributes to peptide binding groove
both alpha and beta
what MHC binds smaller peptides
MHC class I
CD4 (Th cells) recognize Ags presented by class ___ MHC
class II
CD8 (cytotoxic T cell) recognize Ags presented by class ____ MHC
class I
MHC/HLA loci is located on Chromosome
6
______ ______ refers to a discotinuous genetic variation resulting in the occurrence of several different types of individual molecules
molecular polymorphism
class I genes (HLA-A, -B, -C) encode a polymorphic heavy chain which is expressed together with beta2-microglobulin and on the surface of all nucleated cells for Ag recognition by _____ T cells
CD8+
class II genes (HLA-DP, -DR, -DQ) which are expressed on the surface as alpha and beta polymorphic polypeptide chains on APCs for Ag recognition by _____ T cells
CD4+
in class I molecules, the ____ chain is glycosylated
alpha
in class II molecules, the ____ chain is glycosylated
both alpha and beta
_____ ______ on the peptides bind to residues in the class I and class II grooves and vary for different MHC alleles
anchor residues
the cleft of class I molecules are _____ whereas the cleft of class II molecules are _____
closed
open
HLA class II molecules are expressed on
professional APCs (e.g. B cells, dendritic cells, and macrophages)
HLA class I molecules are expressed on
all nucleated cells
expression of MHC class I and/or II molecules is modulated by
cytokines
peptides that bind to class I MHC molecules are derived from ______ microbes that have infected host cells
intracellular
endogenous pathway
peptides that bind to class I MHC are recognized by what cells
CD*+ cytotoxic T cells
Ags and extracellular pathogens taken from the environment are primarily presented on class ____ MHC molecules and presented to what cells?
II
CD4+ helper T cells
function of dendritic cells as APC
naive T cell activation: clonal expansion and differentiation into effector T cells
function of macrophages as APC
effector T cell response: macrophage activation (cell-mediated immunity)
function of B cell as APC
effector T cell response: B cell activation and antibody production (humoral immunity)
_____ is a costimulatory protein found on professional APCs and binds to its ligand ______ which is found on T-cells and is required for coactivation
CD40
CD40L
DCs expression of Class II MHC
constitutive
Macrophage expression of class II MHC
low; induced by IFN-gamma
B lymphocyte expression of class II MHC
constitutive; induced by IL-4
Ags that enter the blood stream are captured by APCs in
the spleen
APCs don’t live in ______ but do live in ______
lymph nodes
spleen
activated NK cells produce ____ during innate immune reactions; this stimulates _____ expression on APCs and thus enhances Ag presentation and activation of CD4+ and CD8+ T cells
IFN-gamma
MHC
B cells require _____ for isotype switching from IgM
CD40/CD40L interaction
how do T cells recognize antigens
recognize only linear peptides
conformation is lost during enzymatic processing of protein Ags into peptides
T cells recognize cell-associated antigens, not _____ antigens
soluble
MHC class II molecules display peptides that are taken up from ______ environment of APCs by mechanisms of either pinocytosis (DCs and B cells) or phagocytosis (macrophages)
extracellular
MHC class I molecules present peptides generated in the proteasome from ______ proteins including proteins from ______ pathogens
cytosolic
intracellular
CD4+ T cells recognize what type of Ags acquired by professional APCs?
extracellular
CD8+ T cells recognize what type of Ags?
Ags derived from intracellular proteins
class I MHC pathway
- production of proteins in the cytosol (virus)
- virus peptides are tagged by ubiquinase and sent to proteosome for proteolytic degradation of proteins
- transport of peptides from cytosol to ER
- assembly of peptide-MHC class I complexes in ER
- peptide-MHC class I complex is sent to Golgi Apparatus to be vesicular
- surface expression of peptide-MHC class I complexes
TAP
transporter to get peptides into ER
class II MHC pathway
- uptake of extracellular proteins into vesicular compartments of APC
- processing of internalized proteins in endosomal/lysosomal vesicles (forms phagolysosome)
- synthesis and transport of class II MHC molecules from ER to endosome
- association of processed peptides with class II MHC molecules in vesicles
- expression of peptide-MHC complexes on cell surface
there are a lot of self peptides synthesized in the ER which are prevented from binding to class II MHC by the ______ chain
invarient
protein HLA-DM removes the invariant chain and allows the ______ of extracellular Ags into class II MHC
loading
the HLA-DM editing mechanism works to ensure the presentation of only the protein fragments most relevant for eliciting an immune response.
HLA-DM has 3 major functions:
HLA-DM causes the dissociation of ______ from the peptide binding groove of MHC II
HLA-DM stabilizes and prevents ______ of the empty MHC II
HLA-DM facilitates the binding of Ag fragments to the ______ stabilized binding groove
CLIP
degradation
open
CLIP is a protein that binds MHC class II and acts as a ______ so nothing else binds to it
placeholder
cross presentation
excellular pathogens get presented to CD8+ T cells via MHC-II
cross-presentation pathway
- some extracellular pathogens brought in b phagocytosis leak into the cytoplasm and are treated as intracellular pathogen
- gets tagged by ubiquitin
- digested by proteosome
- transport of peptides through TAP into ER
- assembly of peptide-MCH I complex in ER
- exocytic vesicle allows for surface expression of peptide-MHC I complex
immunodominant peptides:
immunodominant peptides are obtained by ______ available in the cell
the peptides bind best to the available class I and II MHC molecules
thus, immune responses will be generated against ______ Ags based on the available proteases and MHC molecules
proteases
dominant Ags
why aren’t erythrocytes which don’t express class I MHC not destroyed by NK cells
NK cells spare cells that express “markers of normal self” in the form of MHC class I molecules, and eliminate them when these markers are absent or insufficiently expressed
CD47
glycoprotein consistently expressed on RBCs that serves as a marker of self
CD47 binds to
inhibitory receptor on NK cells
activated Th1 cells help ______ to get rid of ______ microbes and help development of cytotoxic T cells
macrophages
intracellular
cytokine IFN-gamma produced by ______ activated macrophages
Th1 cells
also NK cells
activated Th2 cells are mainly involved in responses against _______ microbes helping _______ cells to develop into memory cells and plasma cells that produce antibodies
extracellular
B
cytokine IL-4 is produced by _______ cells and is important for ______ cell proliferation
Th2
B
