T Cell Development

Front 1

Provide a general description of T cell development
-Be sure to include where they come from

Back 1

-Precursor T cells derived from the lymphoid precursor stem cells in bone marrow migrate to thymus where they mature from immature T cells to mature T cells

Front 2

During the maturation process what will T cells begin to express?

Back 2

It's T cell receptor
CD3
CD4 or CD8
Other accesory molecules

Front 3

What is the TCR

Back 3

It's a membrane bound protein composed of two different polypetides known as alpha and beta chains that are joined toether by a disulfide bond.
There are no secreted forms of TCR

Front 4

What is the structure of the TCR?

Back 4

Alpha and Beta chains expressed at cell surface have one variable region and one constant region
-Valpha and Vbeta combine to form the antigen binding site
-Only one antigen binding site per TCR molecule

Front 5

How many TCR does a single mature T cell have? How many antigens can bind?

Back 5

10^5 TCR on its cell
-The 10^5 TCR on the cell will bind to the same antigen so 10^5 anitgens
-Different T cells have have different versions of TCR and bind to different antigens

Front 6

What provides the antigen specificty for the immune response?

Back 6

the alpha-beta TCR because it binds to an antigen

Front 7

Provide a brief description over the maturation of the thymocytes in the thymus.

Back 7

1) First, developing thymocyte must express a TCR on their cell surface in order to survive, if they don't then they die
2) Thymocytes that have a TCR that cannot recognize self-MHC proteins are not provided with survival signals and die of neglect
3) Thymocytes that express TCR that are able to recognize self-MHC proteins undergo two screening process (Positive Selection or Negative Selection)

Front 8

What cells are permitted to mature after positive selection?

Back 8

Only thymocytes that have a TCR capable of recognizing self-MHC proteins with low affinity are permitted to mature

Front 9

What does negative selection eliminate?

Back 9

Negative selection eliminates thymocytes that have TCRs that recognize self-MHC/self-peptides too strongly

Front 10

What happens to positively selected cells that escape negative selection?

Back 10

They leave the thymus and migrate to peripheral lymphoid organs (lymph nodes and spleen)

Front 11

What is the guarantee of positive selection?

Back 11

It ensures that when the thymocyte matures into a T cell, its TCR would be able to bind to MHC proteins displaying foreign peptides and this allows for the positvely T cells to provide effective immunity against pathogens

Front 12

What is the purpose of positive selection?

Back 12

To select for CD4 or CD8 T cells that can be used for immune responses against foreign antigens particularly pathogens

Front 13

What is the gaurantee of negative selection?

Back 13

It deletes T cells that express high affinity TCRs that are specific for self MHC/self peptides and ensures that mature T cells are not self reactive.

Front 14

It was thought that this mechanism for ensuring T cell tolerance against self-antigens is only effective for self anitgens expressed _________

Back 14

in the thymus

Front 15

Describe the pathway of positive selection

Back 15

1) During T cell development, genes encoding TCRs undergo rearrangement leading to production of immature thymocytes that express a randomly generated TCR repertoire
2) These immature thymocytes express both CD4 and CD8 and are referred to as double positive DP thymocytes
3) By chance a small proportion of DP thymocytes express TCRS will have low affinity for self peptides that are presented by self-MHC molecules
4) Vast majority of DP thymocytes will express TCRs that have little or no affinity for self ligands. Without recieving a TCR signal these DP thymocytes undergo programmed cell death (negelct)
5) Only immature thymocytes that express TCRs with low affinity for self-peptide/self-MHC complexes are positively selected

Front 16

What is the role of AIRE gene
The Autoimmune Regulator

Back 16

It promotes the expression of a wide variety of tissue antigens. It allows negative selection against antigens that are expressed outside of the thymus to be achieved.

Front 17

Where is AIRE expressed in?

Back 17

thymic epithelial cells

Front 18

What are 2 mechanisms for maintaining T cell tolerance to self antigens

Back 18

1) AIRE
2) T regulatory cells

Front 19

Explain the AIRE mechanism

Back 19

1) AIREallows for expression of tissue proteins that are otherwise not found in the thymus (remember that AIRE is expressed in epithelial cells of thymus)
2) Exprssion of these tissue antigens allow negative selection of T cells that express TCRs specific for these antigens
3) Important mechanism for maintaining self tolerance since autoimmune diseases develop in individuals with defect in the AIRE gene

Front 20

What is the function of T regulatory cells?

Back 20

They provide a mechanism for regulating the activity of self reactive T cells that have somehow escaped negative selection

Front 21

How are T regulator cells different from CD4 T cells?

Back 21

T regulatory cells express high levels of CD25 (one part of the receptor for IL2)

Front 22

What do Treg cells do?

Back 22

They suppress immune responses by conventional T cells and they are important for mainitaing self-tolerance since autoimmune diseases develop in inidividuals that are defective in Treg development

Front 23

Describe the structure of a TCR complex

Back 23

It has an antigen binding portion which is made out of:
-TCR alpha and TCR beta polypeptides
-Associated signaling subunit CD3 complex
-Accessory Molecules (CD4 or CD8, but not both)

Front 24

What is the function of the TCR antigen binding subunit?

Back 24

It recognizes peptides that are bound to MHC proteins
-It does not recognize native intact anitgens

Front 25

What is the function of signaling subunit CD3?

Back 25

IT sends signals to the inside of the T cell that activates it and causes it to divide

Front 26

What is the function of the co-receptors CD4 and CD8?

Back 26

It defines the effector function and these molecules bind to the MHC proteins of the APC but at a different siteto the TCR.
-This increases the affinity of interaction between the T cell and the APC