HLA and Antigen Processing Flashcards Preview

MSS-IHL Final Exam > HLA and Antigen Processing > Flashcards

Flashcards in HLA and Antigen Processing Deck (54):
1

histocompatability

first discovered in skin graft transplantation
-genes involved in acceptance or rejection

2

HLA

human leukocyte antigens

-same as MHC (which is in mouse)

3

what do T cells recognize?

need to be presented as a peptide
-by HLA

4

HLA genes

tightly linked and highly polymorphic

5

Class III genes of HLA?

code for complement proteins and cytokines

6

what chromosome are HLA genes on?

chromosome 6 (short arm)

7

HLA haplotype

total set of all HLA alleles on both chromosomes
-have one from mom and dad

-expressed co-dominance - more diversity

important in transplantation (want a match)

8

what does the HLA haplotype allow?

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

9

Class I HLA

three separate regions (membrane bound glycoproteins)
HLA-A,
HLA-B,
HLA-C

present antigen to CD8+ T cells***
expressed on all nucleated cells
-not on RBCs

also inhibitory receptors for NK cells***

10

why don't NK cells kill your RBCs?

???

11

structure of HLA Class I

heterodimer of two proteins

alpha chain encoded by HLA class locus
-alpha 1, 2, and 3
-3 of the 4 globular domains

beta-2 microglobulin is not HLA encoded
-associates non-covalently with alpha 3 domain of alpha chain

12

peptide binding groove of class I?

area between alpha 1 and alpha 2
-binds peptides 8-10 amino acids
-bc it has closed ends

conformation of groove dictates what can bind

each allele has a different range of peptides it can bind

13

what site of Class I HLA has the greatest polymorphisms?

alpha 1 and 2 domains (peptide binding groove)

14

synthesis of Class I HLA alpha chain?

translated into the ER as glycoprotein

interacts with beta-2 microglobulin in the ER and associates with peptides from cytosolic proteins

Class I HLA/peptide complex transported to cell surface

15

how many different HLAs in an individual?

6 different HLAs
all have slightly different shape and present a different set of peptides

16

Class II HLA genes

encoded by the HLA-D region
-HLA-DP, DQ, DR

membrane bound glycoproteins

present to CD 4+ T cells
-primarily on macrophages, dendritic cells, and B cells

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Class II HLA structure?

two proteins
-alpha and beta chain

both encoded in the HLA-D region

four globular domain structure

alpha and beta are not covalently linked

18

location of the binding groove in Class II HLA

alpha 1 and beta 2 domains
-binds 13-18 amino acids (has open ends)

beta 2 is highly conserved (where CD4 binds)

19

range of different Class II HLA?

6-8 possible

20

synthesis of HLA class II

alpha and beta are synthesized in the ER
-invariant chain binds to the alpha and beta chain binds to block the groove

in endocytic compartment - invariant chain degrade
-free peptides then bind in groove

**class II bind peptides that have entered cell via endocytosis (from outside of the cell)

then transported to the cell surfaces

21

alpha and beta chain interactions?

any alpha can associate with any beta chain
-adds to the diversity of peptide binding groove

**greater range of peptides that can bind to class II HLA

22

peptide binding to Class II HLA?

pockets in floor of groove that bind side chains of amino acids on antigen peptide

-rest of peptide bows upward
this is what is recognized by T cells

23

-rates of HLA and antigen association?

slow on rate and very slow off rate
-allows peptide-HLA complex to persist for a long time

24

how many peptides can bind HLA cleft?

only one at a time

25

how many peptides can single HLA cleft bind?

many (but only bind one at a time)

26

H-Y HLA

antigen encoded on Y chromosome
-associated with acute rejection of male grafts in female recipients

27

HLA restriction

ability of T cells to recognize antigen when associated with own HLA
-dual recognition critical to T cell funcion

leads to CD4 only binding Class II and CD8 only binding Class I

28

APC

antigen-processing cells
-convert proteins to peptides for presentation

29

three types of APCs?

macrophages, dendritic cells, and B cells

**other cells can express class II HLA and can act as APCs in some cases (thymic epithelial cells)

30

most efficient APC?

dendritic cells

31

activity of dendritic cell?

pinocytose antigen and process it for presentation

-draw in their dendrites and home to the T cell rich areas in nodes and spleen

activate naive CD4+ and CD8+ T cells

32

macrophage activity?

phagocytose or pinocytose antigen
not as effective as dendritic cells

**activate memory T cells (not naive as well)

33

B cell activity?

bind soluble antigen via surface Ig
-ingest by pinocytosis

bind antigen with high affinity thus effective when antigen low levels

**very effective at presenting to memory T cells

34

antigen capture

microbes enter body and are phagocytosed or pinocytosed by APCs

lose adhesive markers and upregulate CCR7 and increase HLA and B7 expresion

35

what do lymph node and spleen filter?

lymph node - antigens from periphery
spleen - antigens in blood

36

two procesing pathways of the APC?

intracellular - class I
extracellular - class II

37

Class II HLA pathway

exogenous protein ingested and degraded

alpha and beta and invariant chain in ER
-transported through golgi

in late endosome - peptide loaded to the HLA class II

38

fate of the invariant chain?

degraded and leaves CLIP protein behind
-HLA-DM acts as peptide exchanger
-removes CLIP and adds peptide to groove

unbound HLA are not displayed

39

CLIP

fragment left over after the invariant chain is degraded in the Class II binding groove

40

Class I HLA Pathway

for cytosolic antigens
-proteasome - degrades proteins

protein transported to the ER (via TAP - uses ATP)
-ER forms Class I alpha chain
-beta-2 microglobulin associated with TAP via tapasin

in the ER - alpha chain associates with beta-2

41

TAP

transports cytosolic antigen peptides to the ER to form the class I HLA

42

tapasin

binds the beta-2 microglobulin to TAP while HLA class I is forming

43

outcome of dendritic cell antigen presentation?

naive T cell activation

44

outcome of macrophage antigen presentation?

effector (memory) T cell activation
-class II
-activation of macrophage
(cell-mediated)

45

outcome of B cell antigen presentation?

effector (memory) T cell activation
-class II
-antibody production of B cells
(humoral)

46

cross-presentation

dendritic cells can ingest virally infected cells and display antigen class I and class II

47

what is the major factor limiting transplantation?

HLA

48

large number of autoimmune disease due to what?

HLA mutations

49

ankylosing spondylitis

inflammation of spine

over 88% express HLA-B27 allele
-each allele has a limited number of peptides it can present

possible HLA-B27 doesn't present critical peptide

50

rheumatic fever

can lead to antibodies agains cardiac tissue

HLA-DR4 allele involved

51

Sjogrens syndrome

associated with HLA-DR3
-defects in salvation and lacrimation

52

Insulin-dependent diabetes mellitus

associated with HLA-DQw8

53

psoriasis

associated with HLA-B3

54

every immune response is polyclonal

see different part of antigen every time you respond to it

ex/ hepatitis
-display different pieces of the virus

immune response is not one and done**