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IHL Exam 2 > HLA and antigen processing > Flashcards

HLA and antigen processing Flashcards

1
Q

HLA

A

Human leukocyte antigens

function as antigen presenting structures to t cells b/c T cells do not recognize antigens in free or soluble forms

Differences in HLA molecules expressed by an individual will influence the repertoire of antigens to which T cells can respond

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2
Q

HLA gene

A

highly polymorphic (many different alleles are present in the population)

more than 150 separate alleles

Has class II, class III and class I regions

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3
Q

what does class III code for?

A

cytokines and complement proteins

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4
Q

HLA haplotype

A

the total set of HLA alleles present on each chromosome

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

most humans heterozygous with two haplotypes (one from mom and dad)

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5
Q

Co-dominant expression

A

both parental haplotypes expressed simultaneously (so 6 different alleles)

this generates more diversity by increasing the number of different MHC molecules that can present peptides to T cells

very important in transplant b/c want the best match between recipient and donor for both class I and class II genes

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6
Q

MHC class II expressing cell types

A

Dendritic cells
macrophages
B cells

CD4 T helper cells interact with these cells

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7
Q

MHC class I expressing cell types

A

All nucleated cells

CD8 CTLs can kill any virus-infected cell

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8
Q

Gene regions encoding Class I HLA

A

HLA-A
HLA-B
HLA-C

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9
Q

Class I HLA

A

expressed on all nucleated cells

present antigen to CD8+ cytotoxic T cells

in innate immunity –> functions as the inhibitory receptor for NK cells

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10
Q

RBC’s

A

don’t have nucleus

RBCs do not express the activating ligand for NKs so not expressing the inhibitory ligand (Class I HLA) is irrelevant.

if you can’t start the process you don’t have to worry about inhibiting it

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11
Q

where is greatest polymorphism in Class I HLA? what is unique about it

A

in the peptide binding groove b/w alpha 1 and alpha 2

binds peptides about 8-10 aa in length and cannot bind any bigger b/c it has closed ends

each allele of Class I HLA has a different range of peptides that can bind in the groove so when coexpressing all alleles can bind a greater number of peptides

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12
Q

what is unique about the alpha 3 domain of the class I HLA

A

is not polymorphic, conserved amino acid sequences b/c this is where the TCR coreceptor CD8 binds so it has to be the same for everyone

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13
Q

Beta2 microglobulin portion of the Class I HLA

A

Non HLA encoded

same for everybody!

associates non-covalently with alpha 3 domain (NOT Covalently)

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14
Q

Class I HLA structure

A

alpha chain- 3 of 4 globular domains, HLA encoded

beta domain- non HLA coded

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15
Q

Class II HLA

A

aka D region

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16
Q

genes encoding HLA Class II

A

HLA-DP
HLA-DQ
HLA-DR

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17
Q

Class II HLA

A

Primary on antigen presenting cells (macrophages, dendritic cells and B cell)

presenting antigen to CD4+ Tcell

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18
Q

Structure

A

alpha and beta chains both encoded by HLA-D gene region

alpha and beta genes are strongly associated but NOT covalently linked

peptide binding groove between alpha and beta change is the site of the greatest polymorphism

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19
Q

what is unique about the beta 2 region on the Class II HLA

A

this is highly conserved b/c this is where CD4 binds

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20
Q

what is unique about the peptide binding groove in class II HLA

A

formed at the junction of beta 1 and alpha 1

binds peptides between 13 and 18 aa long

OPEN ENDS allow larger peptides to bind

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21
Q

how many class I molecules can be expressed on cells?

A

Because there are three polymorphic class I genes, called HLA-A, HLA-B, and HLA-C in humans, and each person inherits one set of these genes from each parent, any cell can express six different class I molecules

22
Q

what is unique about the synthesis of class II HLA

A

synthesized in the ER and interact with a third protein called the invariant chain

helps keep alpha and beta together

also blocks peptide binding groove until reaches endocytic compartment

in the endocytic compartment invariant is degraded, peptide comes in from endocytosis, binds to class II

23
Q

where do peptides that present on MHC class II come from ?

A

outside world

24
Q

where do peptide that present on MHC class I come from ?

A

cytosol (inside world)

25
Q

Class II HLA features of diversity/genetic polymorphism

A

any alpha chain allele may associate with any beta chain allele, which leads to a greater range of peptides that can bind to class II HLA

26
Q

Peptide binding of peptide binding groove

A

looking for size and shape of Peptide

the rest of the peptide that is not bound (the lateral surface or side of the peptide) sticks out of the cleft and this is what is recognized by antigen receptors on T cells

27
Q

how many peptides can an HLA molecule bind at a time?

A

one

28
Q

antigenic peptides and HLA association

A

slow on rate and very slow off rate

saturatable and low affinity interaction

29
Q

how many peptides can an HLA bind?

A

same molecule of HLA can bind multiple epitopes but NOT at the same time

30
Q

HLA restriction

A

The ability of T cells to recognize antigens when associated with the organism’s own HLA haplotype, providing a dual recognition system critical to T-cell function.

CD4 –> recognize Ag bound to Class II
CD8–> recognize Ag bound to Class I

31
Q

Class I HLA synthesis

A

alpha chain translated into ER as glycoprotein

in the ER alpha chains interact with B2 chains

class I associates with peptides derived from cytosolic (internal) proteins

HLA/peptide complex transported to the cell surface

32
Q

APC’s

A

Antigen presenting cells

Convert proteins to peptides for display

Three main types:
Macrophages
Dendritic Cells
B cells

Thymic epithelial cells can also express Class II HLA during T cell maturation

33
Q

Dendritic cells

A

most effective at presenting antigen

pinocytose Ag and process it for presentation

home to T cell rich areas in lymph nodes and spleen

produce co-stimulatory molecules

activate naive CD4 and CD8 t cells

34
Q

Macrophages

A

Pinocytose or phagocytose

very good at activating memory T cells

35
Q

B cells

A

bind soluble Ag via IgM and IgD

ingest by pinocytosis

bind Ag with high affinity b/c highly specific, thus effective when Ag levels are low

not effective at presenting Ag to naive T cells

very effective at presenting to memory T cells

36
Q

Capture of antigens

A

Microbes enter body

Phagocytosed or pinocytosed by APC’s

lose adhesive markers and up regulate CCR7

increase expression of HLA (Both I and II) and B7

37
Q

HLA-DM

A

acts as a peptide exchanger, facilitating the removal of CLIP and addition of peptides into class II HLA

38
Q

Ii (invariant)

A 
occupies the peptide binding cleft of HLA class II 
promotes folding, assembly, trafficking

is degraded to CLIP by lysosomal enzymes

39
Q

TAP

A

transports peptides from cytosol to interior of ER

functions in the pathway of Class I MHC antigen processing

40
Q

Tapasin

A

B2 microglobulin is bonded to TAP by this tapasin protein

makes sure there is a class I molecule ready to receive a peptide

41
Q

Outcomes of Antigen presentation

A

Dendritic cells–> naive T cell activation
-differentiation into Effector T cells

Macrophages–> effector T cell activation
(cell-mediated immunity) activation of macrophages

B cell–> effector T cell activation
B cell activation and antibody production (humoral immunity)

42
Q

Cross presentation

A

Dendritic cells ingest virally infected cells and display Ag to CTL (via class I) and Ths (via class II)

43
Q

what two effector mechanisms are best able to eliminate microbes that are internalized from the extracellular environment?

A

T helper cells help B lymphocytes produce antibodies

T helper cells help phagocytes to destroy ingested microbes

these are both done with the use of cytokines!!

neither of these mechanisms (which are of the class II/CD4 + pathway) are helpful in elminating viruses and other pathogesn that survive in the cytoplasm

44
Q

what is the mechanism that is most effective for eliminating cytoplasmic microbes?

A

Class I–associated peptides are recognized by CD8 + T lymphocytes, which differentiate into CTLs. The CTLs kill the infected cells and eradicate the infection,

all nucleated cells can be infected with some virus so they all must have class I MHC molecules in order to kill that virus/infection

45
Q

Ankylosing spondoylitis

A

Inflammation of spine
individuals (88 percent) express HLA B27

possible that HLA-B27 doesn’t present a critical antigenic peptide

46
Q

Rheumatic fever

A

generation of antibodies react against streptococci as well as heart tissue

pt’s who have the HLA-DR4 allele

47
Q

Sjogren’s syndrome

A

associated with HLA-DR3

Defect in salivation and lacrimination

48
Q

Insulin dependent diabetes

A

associated with HLA-DQw8

49
Q

Psoriasis

A

Associated with HLA-B3

50
Q

Processing defects?

A

leads to cancers

neuroblastoma

renal carcinoma–> class I antigen processing

51
Q

non-responder

A

if you do not have the genetics that allow a certain peptide to be bound in the peptide binding groove….the T cells can never respond to the antigen b/c they can never see it and nothing can be done about this

52
Q

every immune response is poly-clonal why?

A

because you are seeing different parts of the antigen as it is being processed

so have many different antigen peptides presented for one antigen/infection/virus

IHL Exam 2 (14 decks)

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