MHC and Ag Presentation Flashcards
MHC stands for
Major Histocompatibility Complex
what are the types of MHC
MHC class I and II
what is another name of MHC
transplantation antigens
describe MHC class I structure and binding
one polypeptide chaina nd b/w two regions of that same chain you bind the peptide
describe MHC class II structure and binding
one polypeptide and a separate polypeptide and b/w those two polypeptides you bind the peptide
human version of MHC is called
HLA
class I has what HLA
HLA A
B
C
Class II HLA ha
HLA - DR
HLA-DP
HLA-DQ
what is the primary function MHC gene
to present antigenic peptides
normally MHC genes are presenting
self
CD4 (T-helper) see antigen on surface of
MHC class II
CD8 see antigen on surface of
MHC I
CD8 and you’re sick and you’re attacking chances are what is it attacking
it’s a virus
draw out CD8 binding MHC class I
pg 8
draw out CD4 binding MHC class II
pg 8
CD4 is
helper T cell
CD8 is
killer T cell
the 3d structure of MHC class I requires presence of what to work correctly
beta2 microglobulin
what three genes code for MHC class I polypeptides
HLA-A, HLA-B, and HLA-C
HLA stands for
human leukcoyte antigen
beta2 microglobulin
it is a part of MHC class I, needed for it to function it is encoded for gene at another location thatn the alpha chain
MHC II composed of
two polypeptide chains: alpha & beta
if you’re not sick what will MHC bind
self
if you are sick what will MHC bind
whatever antigen
different MHC II that we have
HLA-DP, HLA-DQ and HLA-DR
where do we have MHC I
everywhere BUT RBC (no nucleus)
basically all cells with nucleus
where will we not have MHC I
RBC
MHC protein is expressed ____ on cell surface
codominantly
what does codomoinantly mean in regards to MHC class I
mom: abc
dad: abc
we express from both parents equally
MHC class II expressed on what cells
B cells
Macrophages
Dendritic cells
(all APC)
MHC II are expressed _____
codominantely
human MHC class II isotypes
HLA-DP
HLA-DQ
HLA-DR
how polymorphic is insulin
not. it is very conserved b/w us and even b/w species
MHC is the most ______ thing we know of
polymorphic
what is the most polymorphic thing we know of
MHC (HLA for humans)
define allele
different forms of a gene; many genes have multiple alleles
define homozygote
alleles at a locus are the same
define heterozygote
alleles at a locus are different
define co-dominant gene expression
all alleles for a particular gene locus are expressed in an individual
define haplotype
a set of alleles of a group of closely linked genes which are usually inherited as a unit.
HLA genes are expressed
co-dominently
what can often happen regarding haplotypes of paternal and maternal alleles
they can recombine their alleles and child would get a mixture of the genes and create a brand new haplotype
compare and contrast homozygote for MHC vs. heterozygote for MHC
pg 18
in terms of MHC II you can create
trans molecule
trans molecule
ex: HLA-DP
alpha chain maternal, beta chain paternal. can potentailly mix apha maternal with beta paternal and create completely new set
the more variable for MHC the more
different pieces it can present or put in the space to present
you want to fit what into MHC
a lot of different proteins, a HUGE amount, so you need MHC to be incredibly diverse
HLA class 1, the α3 region is
identical in all of them
HLA class I α1 α2 are
very variable b/w the MHC
what is holding on to the epitope in HLA
beta sheets
what is surrounding the beta sheets in HLA
alpha helixes
HLA needs to interact w/
interacting with peptide or interacting with TCR
in position 2 of HLA-A binding motif always
leucine or methionine
in position 6 of HLA-A binding motif always have
valine
positino 9 of HLA-A binding motif always have
leucine or valine
peptide binding motif
speicif aa that is anochor
it needs certain aa at certain locations in order for peptide to bind
what is example of HLA-A peptide that binds class I
HIV reverse transcriptase
T cells recognize
short peptidees
the bound peptide belongs to the binding motif for HLA-A*02:01, could you bind a different peptide outside of HIV reverse transcriptase?
yes, it is a pretty general recognition. it just needs certain things in certain binding motifs.
class I MHC is very limited on what
size that can fit - has to be 9 aa
MHC class II is different than MHC I regarding size b/c
they have oepn ends and can fit more aa
what are anchor residues for MHC I
3,5,8
what are anchor residues for MHC II
1,4,6
where will MHC domains participate in binding in MHC class I
alpha 1 and alpha 2
where will MHC domains partiicpate in binding in MHC II
alpha 1 and beta 1
CD1 is similar ot
class I MHC
CD1 is family of
MHC class I encoded outside the MHC
CD1 presents what
microbial lipids
CD1 present microbial lipids to
CD1-restricted T cells - NKT cells
natural killer cells!
if APC present non-self or altered self, what happens
immune response initiated
ultimate goal of MHC I
present non-self or altered self to result as a target cell
APC
dendritic
activated macrophages
b cells
B7 is going to be on surface of
APC
B7-1 is what CD
CD80
B7-2 is what CD
CD86
CD28 is on surface of
T cell
B7 will bind to
CD28 on T cell
what is the first signal that happens for everything for immune response
binding antigen
TCR sees epitope and portion of
MHC presenting
antigen processing
proteolytic degradation
make large proteins into small peptides (and some lipids)
antigen presentation
display
display bound to MHCI or II on surface of APC
MHC-restriction recognition
processed and presented antigens in the context of MHC
molecules are recognized by specific T cell receptors (TCRs)
Antigens are presented by MHC I to CD8+ T cells
Antigens are presented by MHC II to CD4+ T cells
CD8 are
MHCI restricted
Class I is CD8 restricted b/c it requirs
CD8 receptor binding to class I
MCH II restrictd to CD4+ b/c
it requires CD4 receptor binding to MHCII
MHC class I
cytosol
MHC Class II
endocytic vesicles
when macrophage is presented what does it do when presented from class II
it becomes a better macrophage and activates more macrophages
give summary of class II infection
Big picture: infection, exracellular. Probalby bac. Take it in via endocytic vesicle, chop into pieces, miss with lysosome, bring MHC II and combine the two vesicles (one with pieces with MHC II) and express it on the outside. The origin of peptide was extracellular infection
give summary of class I infection
Class I
Got virus, virus makes copies of itself inside cell. In cell have mechanism for degrading proteins: proteasome, it becomes little pieces, now have mechanism to take the little pieces into ER, in ER have MHC I and it combines with protein pieces (epitope) and then go to cell and express
which MHC calss is intracellular origin
class I
which MHC class is extracellular origin
class II
lysosomes
special organelle containing proteases and other hydrolytic enzymes
very acidic
Endosomes/Phagosomes:
acidic vesicles containing foreign proteins and proteolytic enzymes
they bring in the foreign proteins
when the vesicle take in the bac. what will happen as it goes through the cell
there are pumps that make the vesicle containig the bac. (or whatever else) acidic which helps it to degrade the protein
vesicle containing class II molecule called
MIIC
what is MIIC
the actual vesicle that joins with the epitopes
when making MHC II there is alpha and beta chain, is the space open while it is being made?
no - invariant chain is blocking the peptide binding site
what blocks MHC II epitope binding site in ER
invariant chain
what is second role of invariant chain
guides to wherever the acidic vesicles are to fuse with phagolysosome.
after invariant chain blocks things from entering MHC II what happens to it
chop it into pieces except for the CLIP
what is CLIP
a little part of the original invariant chain that is still blocking the epitope binding site of MHC II
what are two roles of invariant chain
blocks MHC II binding site
brings (traffics) it to endosomes
once MHCII is bound to endosome and is surrounded by epitopes, what happens
HLA-DM comes in and helps exchange CLIP for peptide
role of HLA-DM is to facilitaet
removal of clip
finding of the perfect epitope that will fit into peptide-motif
what is key HLA involving in peptide exchange
HLD-DM
HLA-DM works with what
HLA-DO
MHC class II compartment is
MIIC
li stands for
invariant chain
where do MHC I peptides originate
cytosol
MHC class I is
tissue specific
why is MHC I tissue specific
b/c the viruses will target specific cells - there is specificity int erms of tissue by virus
explain MHC Class I pathway
Virus enter cell, replicates, get proteins that are made in cytosol, so the protein is made in our own cells cytosol, proteasome, chops the protein made by viral mRNA into pieces, peptide piece brought into ER, LHA class I with peptides will be expressed on surface
endogenous means?
having an internal cause or origin
infectious virus can be presented in which class
I or II
MHC I has what kind of foreign Ag
exogenous
in MHC I what kind of proteasome takes in the virus protein
immunoproteasome
what is function of proteasome
normally our cells are disposed uneeded or damaged proteins its degraded by proteolysis
IFN gamma induces expression of
immunoproteasome
what is cap of immunoproteasome
PA28 cap
describe immunoproteasome
it is more efficient and works faster than the regular proteasome, activated by IFN gamma
TAP stands for
transporter associated with antigen processing
TAP 1 and TAP 2 requires
ATP
TAP facilitates
peptides that are virus to be taken to immunoproteasome
what upregulates expression of TAP
IFN gamma
when you look at MHC I it’s single chain α and second molecule that for 3 D expression is needed, what is it
ß2m
beta 2 microglobulin
what is essential for expression of MHC I
ß2m
it won’t be expressed without it
peptide binding in MHC I
peptide binding in MHCI α1 & 2
calnexin does what function
holds MHC I until ß2M arrives
what is purpose of life for MHC I
to hold a pathogen epitope for T cell
TAP facilitates transport of peptides from cytosol to
ER
tapasin facilitates
putting peptides into MHC b/w α1 and α2
tapasin, what is analgous protein in MHC II
HLA-DM
b/c peptide loading faciliated by HLA-DM in MHC II
test question!!
if peptides loaded into MHC I and they are too long
ERAP comes and trims the peptide from amino end
MHC I needs what length peptide in it
b/w 8 and 10
what does ERAP stand for
ER aminopeptidase
what does ERAP do
chop up peptide that is too long on MHC I from amino end
presenting self is great unless
you are doing transplant - that would be what is recognized in organ rejection
chances are if it is an intracellular antigen it is a
virus
certain drugs will neutralize the pH of endosomes, what does this do
block processing and presentation of MHC II
non-structural proteins of virus are not recognized by
are recognized by
not recognized by CD4
are recognized by CD8
cross-presentation
great example is hepetitis - b/c it only infects liver answer to question is that you would take dying liver cell and take entire liver cell adn in the phagolysosome you continue class II pathway but some can escape and enter ER - so it does both class I and class II pathways
cross presentation is specific to which cells
dendritic cells
some viruses learn how our body works and have found ways to
interfere with antigen presentation by MHC class I molecules
what are immunoevasins
produced by viruses to interfere with presentation of MHC I to interfere with our immune system
some bacteria evade MHC II - how
escape endoosmes
neutralize endoosme acidification
block fusion with lysosome
sequester MHC II after vesicle fusion
CD1 think
lipid antigen
CD1 is similar to
MHC I
instead of presenting protein CD1 function is
to turn on T cell that will see lipid antigen instead of protein epitope
NKT cell
natural killer t cell
CD1 present to what
NKT & gamma delta T cell
normally CD1 binds self
glycolipid in ER
ultimately CD1 will express what on surface
lipid
