Chapter 5: Antigen Recognition By T Lymphocytes

Question 1

What are antigens?

Answer 1

• chemical substances capable of mobilizing the immune system and provoking an immune response
• microbes or microbial parts
• stimulate T- and B- cells
• antibodies produced by B-cells react against antigens
• one T-cell, B cell, antibody is recognized by one kind of antigen

Question 2

Hapten

Answer 2

• small organic molecule that is not itself antigenic but that may become antigenic when bound to a larger carrier molecule

Question 3

Antigenic Determinant or Epitope

Answer 3

• part of the antigen that stimulates immune system activity

Question 4

T-Cell Receptor Diversity

Answer 4

• is generated by gene rearrangement (SOMATIC RECOMBINATION)
• resembles a membrane-associates Fab fragment of immunoglobulin
• membrane-bound heterodimer composed of an alpha chain of 40-50 kDa and a beta chain of 35-46 kDa
• extracellular portion contains a C-domain and a V-domain

Question 5

Short cytoplasmic Tails

Answer 5

• are expressed on alpha and beta chains

Question 6

T-Cell Germline DNA Gene Rearrangement is…

Answer 6

• exactly similar to that of B-cells before antigen stimulations

Question 7

After Antigen Stimulations?

Answer 7

• there is NO T-cell gene rearrangement

- THIS IS THE DIFFERENCE between T and B cells

Question 8

RAG Genes

Answer 8

• key elements in the origin of adaptive immunity
• important in B cell and T cell diversity
• components of transposon could have evolved to become the RAG genes and the recombination signal sequences of immunoglobulin and T-cell receptor genes
• NO RAG NO ADAPTIVE IMMUNE SYSTEM=== SCIDs disease

Question 9

CD3 Complex

Answer 9

• expression of the T-cell receptor on the cell surface requires association with additional proteins (CD3) to anchor it down

Question 10

The functional antigen receptor on the surface of T cells is composed of ________ polypeptides and is called the ______________________ complex.

Answer 10

• 8

- T-cell receptor complex

Question 11

The alpha and beta chains bind antigen and form the core T-cell receptor (TCR) which associate with one copy of each of…

Answer 11

• CD3y and CD3__ and two copies of each CD3e and the ___ chain

Question 12

There are two more distinct populations of T cells expressed through the receptors

Answer 12

• gamma and delta chains
• only compromise 5% of T cells
• aren’t restricted to MHC molecules/presentation

Question 13

Before T cell encounter w/ antigen…

Answer 13

• T-cell receptor repertoire exceeds Ig of B cell diversity
• T cells have a single binding site for antigens
• B cells have multiple
• T cells do not change their receptors after encounter with antigen
• B cells do change their receptors after encounter with antigen
• No isotype switching or somatic hypermutation in T cells, B-cells do

Question 14

T-cell receptors must recognize antigens bound to…

Answer 14

• cell surface-molecules

Question 15

TCRs and coreceptors allow T cells to recognize and bind to…

Answer 15

• the major histocompatibility complex (MHC)

- which are unique for nearly all individuals

Question 16

Class 1 MHC proteins are found…

Answer 16

• on the surface of nearly all the body’s cells

Question 17

Class 2 MHC proteins are found…

Answer 17

• on the surface of immune cells present (present antigen fragments to naive T cells or APCs)

Question 18

Human Leukocyte Antigen (HLA)

Answer 18

• human MHC

- HLA 1 and HLA 2 = MHC 1 and MHC 2 respectively

Question 19

Multigene Families and Genetic Polymorphism

Answer 19

• diversity of MHC molecules in the human population is due to this
• immunoglobulin and T cell receptor genes, MHC 1/2 genes have a conventional organization and do not rearrange or undergo somatic mutation

Question 20

____ MHC Class1 isotypes and ____ MHC Class2 isotypes in humans…

Answer 20

• 6

- 5

Question 21

MHC molecules have highly promiscuous binding sites for peptides

Answer 21

• an MHC molecule is therefore usually able to present a diversity of peptide antigens to a large number of T cell receptors with highly specific binding sites

Question 22

MHC Polymorphism

Answer 22

• affects the binding and presentation of peptide antigens to T cells
• triggers T-cell reactions that can reject transplanted organs
• the polymorphism of the MHC of organs/tissues transplanted between individuals of different MHC provoke a strong T-cell response directed against the foreign MHC molecules

Question 23

Of the human MHC Class 1 isotypes, which are highly polymorphic?

Answer 23

• HLA-A, HLA-B, HLA-C
• they present peptide antigens to CD8 T cells and interact w/ NK cell receptors
• HLA-E and HLA-G are oligomorphic and interact w/ NK cell receptors
• HLA-F is intracellular and of unknown function, occurs as a single isotype

Question 24

Of the human MHC Class 2 isotypes, which are polymorphic and present peptide antigens to CD4T cells?

Answer 24

• HLA-DP, HLA-DQ, HLA-DR
• HLA-DM and HLA-DO occur in a few isotypes, are intracellular, and regulate the loading of peptides onto HLA-DP, HLA-DQ, HLA-DR

Question 25

Most human cells express MHC Class 1

Answer 25

• only selected cell types express MHC class 2

- expressed on almost all nucleated cells, although they are more abundant on hematopoietic cells

Question 26

MHC Class 2 molecules are normally expressed by only a subset of Hematpoietic cells

Answer 26

• by stromal epithelial cells in the thymus, although they can be produced by other cell types on the exposure to the cytokine interferon-gamma

Question 27

Activated T-cells express MHC class _____ molecules whereas resting T cells do not.

Answer 27

• 2

Question 28

Most cell types in the brain are MHC class 2-____________, but microglial cells (which are closely related to macrophages), are MHC class 2-____________.

Answer 28

• negative

- positive

Question 29

The two classes of MHC molecules have….

Answer 29

• similar 3-D structures

Question 30

MHC Class 1 Molecules

Answer 30

• composed of one membrane-bound heavy chain and noncovalently bonded beta2-microglobulin
• heavy chain has 4 extracellular domains (alpha 1, 2, and 3) which the amino-terminal alpha1 and alpha2 domains resemble each other in structure and form the peptide binding site

Question 31

MHC Class 2 Molecule

Answer 31

• composed of 2 membrane-bound chains, an alpha chain and a beta chain
• these have two extracellular domains each, the aminoterminal 2 (alpha 1, beta 1) resembling each other in structure and forming the peptide-binding site

Question 32

MHC Class 1 Molecules bind to CD8

Answer 32

• the co-receptor binds to the alpha 3 domain of the MHC class 1 heavy chain

Question 33

MHC Class 2 Molecules Bind to CD4

Answer 33

• the co-receptor binds to the beta2 domain of the MHC class 2 molecules

Question 34

T cell Receptor specifically recognizes…

Answer 34

• both peptide antigen and MHC molecule

Question 35

Peptides generated in the cytosol are transported into the endoplasmic reticulum where…

Answer 35

• they bind to MHC Class 1 molecules

Question 36

Peptides presented by MHC Class 2 molecules are generated…

Answer 36

• in acidified intracellular vesicles

Question 37

MHC Class 1 Processing for Antigen Presentation…

Answer 37

• proteins of the peptide-loading complex aid the assembly and peptide loading of MHC Class 1 molecules in the endoplasmic reticulum
• amino-peptidase in the ER can trim peptides bound to MHC class 1 to improve their binding affinity

Question 38

MHC Class 2 processing for antigen Presentation…

Answer 38

• the invariant chain prevents peptides from binding to an MHC class 2 molecule until it reaches the site of extracellular protein breakdown