Lecture 4

Question 1

What is the overall structure of an anitbody/Ig molecule?

Answer 1

• heterotetramer

- 2 identical heavy chains and 2 identical light chains covalently linked together by disulfide bonds

Question 2

Which regions of the antibody structure contact the antigen?

Answer 2

-hypervariable or complementarity determining regions (CDR1, CDR2, and CDR3)

Question 3

Which structure of the amino acid is the isotype?

Answer 3

-amino acid sequence of the H chain

Question 4

What are the five Ig classes?

Answer 4

-IgA (2 subclasses), IgD, IgE, IgG (4 subclasses), and IgM

Question 5

What are the soluble forms of Ig?

Answer 5

• IgD, IgE, and IgG as monomers
• IgA as a dimer
• IgM as a pentameter

Question 6

How are IgA dimers and IgM pentameters held together?

Answer 6

J chain

Question 7

What is the main function of the Fc?

Answer 7

• comprised of 2 carboxyl-terminal domains of 2 heavy chains

- mediating effector functions

Question 8

What is the function of the Fab?

Answer 8

-contains variable regions of antibody and binds to complementary antigen

Question 9

What is the structure of the TCR molecule?

Answer 9

-hetero-dimer with alpha and beta chain

Question 10

antigen

Answer 10

-elicit adaptive (T and/or B cell) immune response

Question 11

epitope

Answer 11

-contacts antigen receptor

Question 12

How do T cells interact with antigen?

Answer 12

• interact with antigen-derived peptides presented in context of self-MHC molecule
• CDR1 and CDR2 regions of TCR interact with MHC
• CDR3 contacts peptide

Question 13

What is the difference between MHC class I and MHC class II?

Answer 13

• MHC class I is expressed on all nucleated cells
• MHC class II expression is limited to antigen presenting cells such as dendritic cells, macrophages, and B cells
• also expressed on thymic epithelial cells

Question 14

single highly polymorphic MHC alpha chain non-covalently associated with non-polymorphic protein beta-2 microglobulin

Answer 14

MHC class I

Question 15

non-covalently associated heterodimer between polymorphic alpha chain and beta chain

Answer 15

MHC class II

Question 16

For MHC molecules where is the peptide antigen presented to T cell receptor?

Answer 16

peptide binding cleft

Question 17

How is the cleft formed for MHC class I?

Answer 17

folding of first two domains of the class I alpha chain

Question 18

How is the cleft formed for MHC class II?

Answer 18

first domain of alpha chain plus first domain of beta chain

Question 19

What is the human MHC also referred as?

Answer 19

HLA- human leukocyte antigen

Question 20

What are the 3 loci which encode distinct human HLA/MHC class I proteins?

Answer 20

• HLA-A, HLA-B, and HLA-C

- each encoding one alpha chain

Question 21

What are the 3 different human HLA/MHC class II loci?

Answer 21

• HLA-DP, HLA-DQ, HLA-DR

- each encoding a distinct alpha and beta chain

Question 22

What are anchor residues?

Answer 22

amino acid residues at critical positions to allow it to fit into binding pockets located in the floor of MHC peptide-binding cleft

Question 23

What are TCR contact residues?

Answer 23

Amino acid residues facing away from MHC molecule interact with TCR

Question 24

How many different MHC I and II proteins can an individual produce?

Answer 24

• 6 for MHC I
• 12 for MHC II
• co-dominant expression for each individual is more likely to have at least one protein capable of presenting a given peptide

Question 25

What is the greatest contributer to rejection in organ and tissue transplantation?

Answer 25

Disparity in MHC sequences

Question 26

Why are CD4 and CD8 co-receptors?

Answer 26

-bind to same MHC molecules as ones engaged by TCR

Question 27

Explain the mechanism for MHC class I pathway.

Answer 27

- peptides derived from intracellular pathogens - proteosome degrades protein into peptides - peptides transported across ER membrane by TAP (transporter associated with antigen processing)

Question 28

Explain the mechanism for MHC class II pathway.

Answer 28

- present extracellular derived antigens - APC engulf microbes via phagocytosis/endocytosis - internalized material localizes in endosomes which then fuse with lysosomes - peptides associate with MHC II and traffic to plasma membrane - MHC II interact with invariant chain (Ii) protein which binds to MHC II in ER - MHC II-Ii complex transport to endosomal intracellular vesicle where Ii is degraded by proteases