Chapter Four (Part II)

Question 1

How are the antigen-recognition molecules of T-cells made? What are they associated with?

Answer 1

made solely as membrane-bound protein which are associated w/ an intracellular signaling complex & function only to signal T cells for activation

Question 2

How are TCRs related to immunoglobulins?

Answer 2

in their protein structure - having both V and C regions

Question 3

How do TCRs and BCRs differ?

Answer 3

TCR does not bind antigen by itself but recognizes short peptide fragments of protein antigens that are presented to them by proteins known as MHC molecules on the surface of host cells

Question 4

What are MHC molecules?

Answer 4

transmembrane glycoproteins encoded in the large cluster of genes known as the major histocompatibility complex. highly “polymorphic” - each type of MHC molecule occurs in many different versions - w/i the population (can cause organ rejection)

Question 5

Are most people homozygous or heterozygous for MHC molecules? What does this do?

Answer 5

heterozygous - express 2 different alleles for each type of MHC molecule. increases range of pathogen-derived peptides & self-peptides that can be bound

Question 6

What are MHC molecules encoded by?

Answer 6

slightly different versions of individual genes called alleles

Question 7

What do TCR recognize?

Answer 7

features of both the peptide antigen & the MHC molecules to which it is bound

Question 8

What is MHC restriction?

Answer 8

an “extra dimension” to antigen recognition by T cells because any given TCR is specific for a particular peptide bound to a particular MHC molecule (“tripartite interaction”)

Question 9

How many polypeptide chains in a TCR? What are they called? How many domains does each chain have/

Answer 9

2 (TCR alpha & TCR beta) chains w/ 2 domains each

Question 10

What chains do a minority of TCR with an alt structure have?

Answer 10

γ and δ

Question 11

How do B cells & T cells differ in the antigens they recognize?

Answer 11

B cells recognize native antigens vs. T cells recognize processed antigens

Question 12

What form of antigen do T cells recognize?

Answer 12

form of a complex of a foreign peptide bound to an MHC molecules

Question 13

How do B cells & T cells differs in where their receptors are?

Answer 13

B cells have membrane Ig vs. T cells don’t just have membrane receptors

Question 14

What are the two forms of antigen recognition by the B cell receptor?

Answer 14

1. conformational determinant 2. linear determinant

Question 15

What is conformational determination antigen recognition by BCRs?

Answer 15

relies on the 3D structure of a protein -> determination may be lost by denaturation

Question 16

What is linear determination by antigen recognition by BCRs?

Answer 16

able to recognition linear structures on proteins that have been denatured -> can recognition native and denatured proteins

Question 17

What class of MHC do Tc cells (cytotoxic T cells) recognize? What coreceptor is used?

Answer 17

MHC class I w/ CD8

Question 18

What class of MHC do TH (helper T cells) cells recognize? What coreceptor is sued?

Answer 18

MHC class II w/ CD4

Question 19

What is true about MHC class I and class II molecules?

Answer 19

similar 3D structures but have distinct subunit compositions

Question 20

What is the structure of a MHC class I molecule?

Answer 20

non covalently associated w/ a smaller chain, beta-2 microglobulin

Question 21

What is the structure of MHC class II molecules?

Answer 21

1. 2 transmembrane glycoprotein chains: alpha (34 kDa) & beta (29 kDa) 2. non covalent complex of 2 chains: alpha & beta, both of which span the membrane

Question 22

What is true about the ends of peptides in MHC class I molecules?

Answer 22

peptide is bound in an elongated conformation with both ends tightly bound at either end of the clef: “bound ends”

Question 23

What is true about the ends of peptides in MHC class II molecules?

Answer 23

the peptide is bound in an elongated conformation but the ends of the peptide are not tightly bound & the peptide extends beyond the cleft: “free ends”

Question 24

What happens when peptides are not bound to MHC molecules?

Answer 24

MHC molecules are unstable bc peptide is bound as an integral part of the MHC molecule’s structure. this dependence on bound peptide applies to MHC class I & class II molecules

Question 25

Why is stable peptide binding important?

Answer 25

w/o it exchanges occurring at the cell surface would prevent peptide:MHC complexes from being reliable indicators of infection or of uptake of a specific antigen

Question 26

What is bound at the ends of MHC class I molecules?

Answer 26

short peptides of 8-10 AAs at both ends

Question 27

Where are the main differences between allelic MHC variants found?

Answer 27

certain sites in the peptide-binding cleft resulting in different AAs in key peptide-interaction sites and bc of this different MHC variants preferentially bind different peptides

Question 28

How do peptides bind to MHC molecules?

Answer 28

through structurally related anchor residues. anchor residue differ for peptides that bind different allelic variants of MHC class I molecules

Question 29

Are anchor residues identical?

Answer 29

no but are always related. ex: phenylalanine and tyrosine are both aromatic AAs

Question 30

Are the length of peptides bound by MHC class II molecule constrained?

Answer 30

no, natural peptides that bind are at least 13 AAs long & can be much longer. in most cases they are trimmed by peptidases to around 13-17 AAs. variable in length & anchor residues lie at various distances from the ends of the peptide

Question 31

How does the TCR interact w/ MHC class I and class II molecules?

Answer 31

interacts with both in a similar fashion

Question 32

How do CD4 & CD8 cell-surface proteins of T-cells contact MHC molecules?

Answer 32

make direct contact w/ MHC molecules and are required to make an effective response to antigen

Question 33

What kind of cells express MHC class I molecules?

Answer 33

all nucleated cells although they are most highly expressed in hematopoietic cells

Question 34

What kind of cell express MHC class II molecules?

Answer 34

only a subset of hematopoietic cells

Question 35

How is the expression of MHC class I and class II molecules regulated?

Answer 35

cytokines

Question 36

What cytokine increases the expression of MHC class I molecules on all types of cells?

Answer 36

interferon-alpha (IFN-alpha) and IFN-beta

Question 37

What does INF-gamma do?

Answer 37

increases expression of MHC class I &II molecules & can induce expression of MHC class II molecules on certain cell types that do not normally express them

Question 38

What happens when MHC class I is absent?

Answer 38

allows Plasmodium parasites that cause malaria to live in privileged state

Question 39

What are CD4 and CD8

Answer 39

co-receptors (extra receptors)

Question 40

Describe the structure of CD4.

Answer 40

single-chain protein composed of 4 Ig like domains

Question 41

What do co-receptors do?

Answer 41

binding contributes to overall effectiveness of T-cell response

Question 42

What does CD4 do?

Answer 42

enhances sensitivity to antigen. T cell in 100 fold more sensitive to antigen when CD4 is present. result from ability of intracellular portion of CD4 to bind to cytoplasmic tyrosine kinase called Lck

Question 43

Where does CD8 bind on a MHC class I molecule?

Answer 43

site on MHC class I molecule that is distant from where TCR binds

Question 44

Where are α:β T cells found?

Answer 44

lymphoid tissues of all verts but all in intraepithelial lymphocytes particularly in skin & female reproductive tracts where their receptors display very limited diversity

Question 45

What is different about gamma:deta T cells?

Answer 45

do not generally recognize antigen as peptides presented by MHC molecules & are not restricted by ‘classical’ MHC class I and class II molecules that function in binding and presenting peptides to T cells