1-Antigen Presentation

Question 1

MHC proteins

Answer 1

expressed on surface of nucleated cells to control protein antigens that can be resp to

aka HLA in humans ‘human leukocyte antigen’

Question 2

MHC genetics

Answer 2

haplotype = total set of MHC genes on each chromo so inherit one haplotype from each parent

MHC is polygenic so multi diff genes w/i each indiv

MHC gene expression is polymorphic so multi variants of each gene in a pop and codominant so alleles express simultaneous

Question 3

MHC Classes

Answer 3

Class I proteins = genes A,B,C
Class II proteins = D region genes
-can combo with alpha/beta of other class II’s

3 class I + 3 class II from each parent

Question 4

role of MHC proteins

Answer 4

T lymphocyte response depends on antigen presenting cell has MHC proteins on it

peptides non covalently bound to MHC proteins to localize T cell activation and interact with amino acids on MHC

Question 5

disease associations

Answer 5

1. narcolepsy has HLA-DR2 allele present in 100% pts
2. ankylosing spondylitis HLA-B27 in 90% pts

Question 6

clinical application MHC

Answer 6

1. organ transplant- may be rejected bc non-self MHC recognized as foreign but can type leukocytes for class I and II’s by antisera or molecular techs
   -match HLA + immunosuppress drugs = inc success of long term graft
2. paternity testing- HLA typing of mother, child, alleged father
   -can only exclude father not absolutely include

Question 7

Class I MHC

Answer 7

@nearly all nucleated body cells except RBC since no nucleus

structure: 2 non-covalent linked polypep chains alpha/beta with
peptide binding + transmembrane + cytoplasmic regions
-beta microglobulin required for cellular expression of alpha chain

Question 8

Class I binding mechanism

Answer 8

-peptide binding region holds foreign peptides for recognize by T cell antigen receptor of CD8 T lymphocytes
-cleft only large enough for small fragments of antigen
-ends of cleft pinch in

Question 9

Class II MHC Proteins

Answer 9

@professional APC i.e dendritic cells, macrophages, B lymphocytes

structure: 2 non covalent linked polypep chains alpha/beta each encoded by separate MHC gene
-peptide binding + transmem + cytoplasmic regions

dendritic most potent APC for primary response/activate T cells

Question 10

Class II binding

Answer 10

peptide binding region with foreign peptide recog by CD4 T lymphocytes
-cleft can hold larger fragments than class I bc stays open at ends

Question 11

MHC restriction

Answer 11

CD4 T lymphocytes only recog class II MHC

CD8 T lymphs only recog class I MHC

T lymphs only recog denatured protein antigens bc antigen must be processed and nonproteins won’t bind to MHC

multiply to 8

Question 12

dendritic cells

Answer 12

-produced by bone marrow to circulate in blood then migrate to issues as long lived immature dendritic cells esp in skin
-continuously sample environment via phagocytosis and macropinocytosis
-in nearly every organ of body

Question 13

enhancing class II

Answer 13

1. APC activates T lymphocytes
2. interferon gamma released by T cell
3. inc class II MHC of surface of APC so more APCs to present antigens to T lymphs

Question 14

typical antigen presentation

Answer 14

1. immature dendritic cells take up antigen = activated
2. migrate to nearest lymphoid tissue
3. dendritic cells mature and present antigen to T helper lymphocytes

Question 15

exogenous antigen processing

Answer 15

1. antigen internalized via phagocytosis/receptor mediated endocytosis/ fluid phase pinocytosis
2. class II MHC bound by invariant chain to prevent binding of other cell proteins
3. vesicles fuse with plasma membrane
4. activate T helper
5. antibody production

Question 16

endogenous antigen processing

Answer 16

-nothing intrinsically diff just separate pathway
-class I MHC complexes formed in ER then shuttled to plasma mem of viral infected cell
-antigen peptides transported into ER via TAP protein
-activate CTL vs virus infected/tumor cells

can be cross presented