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

HLA and Antigen Processing Flashcards

1
Q

histocompatability

A

first discovered in skin graft transplantation

-genes involved in acceptance or rejection

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2
Q

HLA

A

human leukocyte antigens

-same as MHC (which is in mouse)

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3
Q

what do T cells recognize?

A

need to be presented as a peptide

-by HLA

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4
Q

HLA genes

A

tightly linked and highly polymorphic

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5
Q

Class III genes of HLA?

A

code for complement proteins and cytokines

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6
Q

what chromosome are HLA genes on?

A

chromosome 6 (short arm)

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7
Q

HLA haplotype

A

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)

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8
Q

what does the HLA haplotype allow?

A

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

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9
Q

Class I HLA

A

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***

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10
Q

why don’t NK cells kill your RBCs?

A

???

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11
Q

structure of HLA Class I

A

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

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12
Q

peptide binding groove of class I?

A

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

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13
Q

what site of Class I HLA has the greatest polymorphisms?

A

alpha 1 and 2 domains (peptide binding groove)

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14
Q

synthesis of Class I HLA alpha chain?

A

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

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15
Q

how many different HLAs in an individual?

A

6 different HLAs

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

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16
Q

Class II HLA genes

A

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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17
Q

Class II HLA structure?

A

two proteins
-alpha and beta chain

both encoded in the HLA-D region

four globular domain structure

alpha and beta are not covalently linked

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18
Q

location of the binding groove in Class II HLA

A

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

beta 2 is highly conserved (where CD4 binds)

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19
Q

range of different Class II HLA?

A

6-8 possible

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20
Q

synthesis of HLA class II

A

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

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21
Q

alpha and beta chain interactions?

A

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

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22
Q

peptide binding to Class II HLA?

A

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
Q

-rates of HLA and antigen association?

A

slow on rate and very slow off rate

-allows peptide-HLA complex to persist for a long time

24
Q

how many peptides can bind HLA cleft?

A

only one at a time

25
Q

how many peptides can single HLA cleft bind?

A

many (but only bind one at a time)

26
Q

H-Y HLA

A

antigen encoded on Y chromosome

-associated with acute rejection of male grafts in female recipients

27
Q

HLA restriction

A

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
Q

APC

A

antigen-processing cells

-convert proteins to peptides for presentation

29
Q

three types of APCs?

A

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
Q

most efficient APC?

A

dendritic cells

31
Q

activity of dendritic cell?

A

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
Q

macrophage activity?

A

phagocytose or pinocytose antigen
not as effective as dendritic cells

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

33
Q

B cell activity?

A

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
Q

antigen capture

A

microbes enter body and are phagocytosed or pinocytosed by APCs

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

35
Q

what do lymph node and spleen filter?

A

lymph node - antigens from periphery

spleen - antigens in blood

36
Q

two procesing pathways of the APC?

A 
intracellular - class I
extracellular - class II
37
Q

Class II HLA pathway

A

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
Q

fate of the invariant chain?

A

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
Q

CLIP

A

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

40
Q

Class I HLA Pathway

A

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
Q

TAP

A

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

42
Q

tapasin

A

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

43
Q

outcome of dendritic cell antigen presentation?

A

naive T cell activation

44
Q

outcome of macrophage antigen presentation?

A

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

45
Q

outcome of B cell antigen presentation?

A

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

46
Q

cross-presentation

A

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

47
Q

what is the major factor limiting transplantation?

A

HLA

48
Q

large number of autoimmune disease due to what?

A

HLA mutations

49
Q

ankylosing spondylitis

A

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
Q

rheumatic fever

A

can lead to antibodies agains cardiac tissue

HLA-DR4 allele involved

51
Q

Sjogrens syndrome

A

associated with HLA-DR3

-defects in salvation and lacrimation

52
Q

Insulin-dependent diabetes mellitus

A

associated with HLA-DQw8

53
Q

psoriasis

A

associated with HLA-B3

54
Q

every immune response is polyclonal

A

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**

MSS-IHL Final Exam (15 decks)

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