Antigen Presentation

Question 1

Antigen presenting molecules use MHCs aka

Answer 1

human leukocyte antigen (HLA)

Question 2

Type I MHC on

Answer 2

all nucleated cells in the body

Question 3

Type II MHC on

Answer 3

professional antigen presenting cells: Dendritic cells, macorphages, B lymphocytes and some thymocytes

Question 4

two receptors for MHC

Answer 4

B cell receptors and T cell receptors

Question 5

T cells do not recognize

Answer 5

antigens in free/soluble forms

Question 6

T cells only recognizes antigens associated with

Answer 6

MHC/HLA

Question 7

differences in HLA/MHC molecules expressed by an individual will influence the

Answer 7

repertoire of antigens to which T cells can respond

Question 8

MHC/HLA has an unprecedented extent of

Answer 8

polymorphism

more then 150 separate alleles have been identified within the MHC

many alternative versions of each MHC gene

Question 9

MHC location is on chromosome

Answer 9

6 and divided into three classes

Question 10

MHC haplotype

Answer 10

encode protein antigens central for immune system to discriminate between self and non self

most humans are heterozygous (one from mom, one from dad) and both are codominant to generate more diversity

Question 11

transplanation

Answer 11

want the best match possible between donor and recipient for both class I and II genes

Question 12

Class I MHC genes

Answer 12

encoded by three separate gene regions in the MHC locus

• HLA-A
• HLA-B
• HLA-C

these are membrane bound glycoproteins
expressed on all nucelated cells
inhibitory receptor for NK cells

Question 13

MHC I

Answer 13

present antigen to CD8 CTL

Question 14

MHC I structure

Answer 14

membrane bound glycoprotein
4 extracellular domains
conserved
heterodimer of a chain and B2 microglobulin

Question 15

MHC 1 a chain

Answer 15

encoded by the MHC class locus

forms three of the fourh globular domains

a1, a2, and a3

Question 16

MHC I B2 microglobulin

Answer 16

non MHC encoded

forms fourth fomain

associates noncovalently with the a3 domain of the a chain

Question 17

the area between a1 and a2 domains of the MHC I has teh

Answer 17

peptide binding groove

greatest polymorphism

peptides are bound and presented on teh surface of cells

bunds pepetides 8-10aa in length

closed ends limit size

Question 18

key features of MHC I

Answer 18

all alleles of class I can be expressed at the same time on each cel (6 different MHCs)

slightly different shape –> present a differnt set of peptides

conformation of this forrve dictates what peptides can bind

Question 19

each allele of class I MHC has a differetn range of peptides that can

Answer 19

bind in the groove

Question 20

synthesis of a chain of MHC I

Answer 20

translated into ER as glycoproteins

Question 21

in the ER, alpha chain of MHC I interacts with

Answer 21

B2 microglobulin and associates with peptides derived from cytosolic proteins

then MHC I peptide complex are transported to cell surface

Question 22

class II genes are encoded by the

Answer 22

HLA-D region with three sets of genes

HLA-DP
HLA-DQ
HLA-DR

Question 23

Class II MHC genes have an

Answer 23

A and B chain
membrane bound glycoproteins
antigen presenting cells only

Question 24

MHC II present to

Answer 24

CD4 T cells

Question 25

MHC II structure composed of

Answer 25

two proteins a chain and b chain, strongly associated four globular domains NOT covalently linked

Question 26

MHC II peptide binding groove

Answer 26

formed by the a1 and b1 globular domains binds peptides 13-18aa long open end allows for larger peptides

Question 27

each allele of class II MHC has a

Answer 27

different range of peptides that can bind in the groove a1 and b1 globular domains have greatest polymorphism

Question 28

in MHC II, all alleles of the a and B chains are

Answer 28

expressed 6a chains and 6 b chains any a chain allele may be associated with any B chain allele adds to the diversity of the peptide-binding groove

Question 29

greater range of peptides that can bind to

Answer 29

Class II MHC

Question 30

antigen-MHC binding is

Answer 30

saturateable and low affinity slow-on rate very slow-off rate

Question 31

slow MHC-antigen binding allows

Answer 31

peptide MHC complex to persist long enough to interact with T cells

Question 32

only one peptide binds to an MCH

Answer 32

at any one time, either I or II same MHC can bind multiple peptides at different times, either I or II

Question 33

peptide bining

Answer 33

there are pockets in the peptide-binding cleft the aa on the antigen peptides fit into these pckets and anchor the peptides in the cleft the rest of the peptide contains residues that bow upward and are recognixed by the ag receptors on T cells

Question 34

antigens coded on Y chromosome

Answer 34

can cause accute rejection on male grafts in female pts

Question 35

capture of antigens

Answer 35

microbes enter the body pahgocytosed by APC in tissues antigens enter via periphery and filtered by the lymph antigens in the blood are filtered by the spleen

Question 36

Professional APC express a lot of

Answer 36

MHC II and costimulatory molexyles can activate naive T cells ex is classical DCs in all tissues plasmacytoid DCs are in blood and tissues, promote innate and antiviral state

Question 37

activation of DC cells

Answer 37

lose adheisve markers and upregulate CCR7 increase MJH and CD80 travel to regional secondary lymphoid tissue mature as they migrate present Ag to T cells

Question 38

two processing pathways

Answer 38

depends on chemical nature of ag density of peptide specific MHC and its binding site self vs nonself

Question 39

each pathway stimualtes the T cell population most effective, I.E.

Answer 39

intracellular pathogens and self: MHC I extracellular pathogens: MHC II

Question 40

MHC II pathway

Answer 40

exogenous proteins are ingested and degraded a and B and invarient chains are made in the ER and sent ot Golgi peptide is not loaded until late endosome

Question 41

invariant chain MHC II pathway

Answer 41

Ii occupies the peptide binding cleft, probotes folding, assembly, trafficking and place holder Ii is degraded to CLIP by lysosomal enzymes HLLA-DM acts as peptide exchanger, remvoing LCLIP and adding peptide to MCH II unbound MHC are no displayed

Question 42

MHC I pathway

Answer 42

cytosolic antigens proteasome foind in cytoplasm of most cells, degrades damaged proteins, and targeted by ubiquitin TAP-transports peptides from cytosol to ER where peptide is trimmed and loaded into MHC I

Question 43

MHCs carry peptides from normal self proteins that are degraded but these do not normally

Answer 43

provoke an immune respone

Question 44

cross presentation

Answer 44

dedritic cells ingest virally infected or transformed cells and display antigens to CTLs can also display to Th cells

Question 45

transplantation

Answer 45

a major factor limiting the success of transplantatino is the imune response of teh recipient to te donor tissue

Question 46

HLA associated diseases

Answer 46

many autoimmune diseases and susceptibilty to infectinos are assocaited with HLA alleles most HLA associated idseases have unknonw etiologies that contribute to the immunologic abnormalities

Question 47

HLA associated disease: ankylosing spondylitis

Answer 47

inflammation over the spine 88% of poeple have HLA-B27 allele each allele has limitined number of peptides it can present possible that HLA B27 allele cnanot bind a critical antigenic peptide or present a critical antigenic peptide against the agent causing the disease

Question 48

HLA associated disease: rheumatic fever

Answer 48

sequela of strep pyrogenes infection generation of ab against the streptococci, cross reacti with cardiac tissue patients with HLA-DR4 allele are more prone

Question 49

other HLA assocaited diseases

Answer 49

Sjorgren's syndrome: associated with HLADr3, defect in salivation and lacrimation insulin dependent DM: associated with HLA-DQ w8 and others psoriasis: associated with HLA-B3

Question 50

class I antigen processing defects

Answer 50

renal cell carcinoma transporter assocaited with antigen processing is down regulated (TAP)

Question 51

bare lymphocytes syndrome (Class I MHC)

Answer 51

TAP protein is nonfunctional, so no peptides can enter the ER class I molecules cannot leave the ER unless they have bound a peptide, cells cannot present antigens on their surface chronic resp. infections, poor responses to viruses

Question 52

bare lymphocyte syndrome class II MHC

Answer 52

caused by inherited decfect in CIITA leading to def. in HLA class II expression on cells and nonfunctioning T cels HLA II genes are turned on by CIITA which induces IFNy. mutations in any Tf lead to decrease in class II gene prpducts reduced Th cell count due to failed thymic selection reduced antigen presentation to mature T cells decreased humoral and CMI repsonses incluting DTH pt have severe recurrent infections