Chapter 6 MHC Molecules and Antigen Presentation to T Lymphocytes Jitt # 4 114 - 124

Question 1

Why are dendritic cells the most efficient APC for initiating primary T-Cell responses? (Four reasons)

Answer 1

1) Dendritic cells are located at the most common sites of entry of antigens (in epithelia) and in tissues that may be colonized by microbes. 2) Dendritic cells express receptors that help them capture microbes 3) DC migrate from epithelia and tissues to lymph nodes. T - Cells migrate to same regions of lymph nodes. 4) Mature DC express high levels of peptide- MHC complexes, costimulators, and cytokines, all of which are needed to activate naive T lymphocytes.

Question 2

Monocytes responsibility in cell-mediated immunity

Answer 2

Monocytes travel to areas of infection and inflammation. There they differentiate into macrophages and phagocytes. CD4+ T cells recognize microbial antigens being presented by the macrophages and provide signals that enhance the microbicidal activities of these macrophages

Question 3

What type of cells can present peptides to CD8+ CTLs?

Answer 3

All nucleated cells can present peptides to CD8+ CTLs

Question 4

What was the importance of using congenic mice to elucidate MHC function.

Answer 4

Congenic have the same genes except the MHC locus. Self cells infected with virus activated CTLs, while infected cells of a different strain did not activate CTLs. This showed that MHC is important in antigen presentation.

Question 5

Which MHC class is related to CD8+? CD4+?

Answer 5

Class I CD8+, class II CD4+

Question 6

What is the difference between Class I MHC expression and Class II MHC expression?

Answer 6

Class I MHC is expressed on almost all nucleated cells, where as Class II MHC is expressed on DCs, B lymphocytes, macrophages, and more

Question 7

What type of antigens do MHC I / CD8+ recognize? Why is this important?

Answer 7

Cells infected with intracellular mirobes, viruses, and cancer laden cells. ( Viral and Tumor Antigens) Antigens are presented on cell surface. This is important because all nucleated cells can become mutagenic or infected with virus.

Question 8

Why does Class II MHC make sense?

Answer 8

Class II MHC is related to CD4+ function. The role of CD4+ is to increase the pathogenic nature of Macrophages, DCs and other phagocytes as they capture extracellular antigens. CD4+ also activate B cells to produce antibodies to eliminate extracellular antigens.

Question 9

Which type of cytokines increase the expression of MHC?

Answer 9

IFN a, b, and g; g is the most abundant IFN in Class II upregulation; cytokines stimulate transcription of MHC molecules.

Question 10

What cells produce IFNg?

Answer 10

NK cells and antigen activated T cells

Question 11

CIITA

Answer 11

Class II transcription activator. Binds to Class II promoter and promotes efficient transcription.

Question 12

Bare Lymphocyte Syndrome

Answer 12

Lack CIITA. causes reduced or absent expression of Class II MHC on DCs and B Lymphocytes. IFN g cannot induce Class II expression.

Question 13

What three structural features are shared by all MHC molecules?

Answer 13

extracellular binding cleft, immunoglobulin (Ig)-like domains, and trans-membrane and cytoplasmic domains

Question 14

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

Answer 14

MHC I is composed of 1 MHC encoded polypeptide chain and a second non-MHC-encoded chain; MHC II is composed of two MHC-encoded polypeptide chain

Question 15

Where are the polymorphic amino acid residues of MHC molecules located?

Answer 15

In and adjacent to the peptide binding cleft. alpha helices make up the walls of the cleft, while the resting floor is made up of beta pleated sheets. This is where peptides bind to and are displayed to T cells. Much variation occurs here, and gives rise to binding diversity.

Question 16

What is the role of non polymorphic Ig- like domains of MHC molecules?

Answer 16

They contain binding site for T cell moleules CD8+ and CD4+. CD4+ binds to MHC II and CD8+ binds to MHC I

Question 17

Structure of MHC I

Answer 17

1) MHC encoded alpha heavy chain and non MHC encoded b2-microglobulin subunit 2) all MHC class I molecules have an a3 immunoglobulin like domain that is conserved. 3) a3 (mostly), b2m, and a small part of the lower portion of a2 contributes to the binding of CD8+

Question 18

b2 microglobulin

Answer 18

Light chain of MHC I; interacts non covalently with a3; invariant among all MHC I molecules

Question 19

Fully Assembled MHC I Trimer

Answer 19

a chain, b2m, and bound peptide; all three must be present. peptides stabilize the b2m and a chain, and peptide binding is strengthened by b2m and the a alpha chain being present.

Question 20

Structure of MHC II

Answer 20

1) Both chains (a and b) are MHC encoded 2) polymorphic residues encoded by a1 and b1 segments four each (the binding cleft is open allowing for 30+ residues to bind) 3) a2 and b2 contributes to CD4+ binding

Question 21

Fully assembled MHC II Trimer

Answer 21

1) a and b chains and bound antigenic peptide

Question 22

What is special about the binding capabilities of MHC molecules?

Answer 22

Both MHC I and II have the capability to bind a numerous amount of different types of peptides, however each MHC molecule can only bind 1 peptide at a time (There is only one peptide binding cleft). This is opposite to lymphocytes who have one receptor for a specific antigen. This is important because there are only 6 types of MHC I molecules and 8-10 MHC II molecules. Cells need to be able to present an enormous amount of antigens

Question 23

Why are T Cells the mediators of immunity to intracellular microbes?

Answer 23

Peptides bound to MHC are placed during their bio-genesis in the cell. MHC I acquire proteins mainly from cytosolic proteins whereas MHC II acquire proteins from intracellular vesicles.

Question 24

Do MHC molecules discriminate between self and foreign peptides?

Answer 24

No. Therefore, MHC molecules display both self peptides and foreign peptides.

Question 25

If there are a crap ton of MHC molecule bound to the surface of a cell, how in the hell do T Cells recognize MHC bound antigens?

Answer 25

1) T Cells are sensitive and only recognize very few MHC-peptide complexes 2) microbes increase MHC expression leading to an increase in the amount of foreign peptides bound to MHC and microbes cause the expression of secondary signals. 3) T cells reactive to self peptides are eliminated

Question 26

What type of binding occurs between MHC molecule and its peptide?

Answer 26

Non covalent interactions between the b strands of the floor and the alpha helices of the walls and the peptide fragments;