T cell development and selection: positive and negative selection

Co-dominant

Alleles for MHC molecules are ________

CD3

Analog of Iga/b in BCR; associates with the pre-TCR for signaling

Positive selection

Cells that bind self-MHC receive a survival signal

Negative selection

Cells that bind self-MHC:peptide complexes too strongly receive a death signal

Bone marrow derived dendritic cells and macrophages in the medulla

Cells used to test self-MHC binding ability of TCR during negative selection

Thymic cortical epithelial cells

Cells used to test self-MHC binding ability of TCR during positive selection

DRalpha and Ealpha in mice

Chain of MHCII molecules that is less variable than others in Humans and mice

Instructive Model

Model of co-receptor selection where the cell can tell the difference between CD4 and CD8 by signal strength. CD8 has a weaker LCK signal. The signal strength determines which co-receptor will fall off

Stochastic Model

Model of co-receptor selection where the cell randomly down regulates on of the co-receptors. There is a 50/50 chance of making a T cell with the correct co-receptor and MHC binding specificity

IL-7R, c-kit, Thy1, and CD44

Molecules induced by the interaction between the lymphoid progenitor and the thymus stroma via adhesion

Thy1

T cell lineage commitment marker

Allelic exclusion

T cell receptor must express from one chromosome and only one type (alpha/beta OR gamma/delta)

Thymocytes

T cells developing in the thymus

Short peptides presented by MHC molecules

T cells only recognize _________

MHC haplotype

Term describing the Class I and Class II alleles on ONE chromosome

MHC polymorphism

Term describing the many alleles for Class I and Class II MHC molecules

VJ

The TCRalpha chain undergoes ___ recombination

VDJ

The TCRbeta chain undergoes ___ recombination

cortico-medullary junction

The part of the thymus where the major selection events occur

Pre-Talpha

The surrogate TCRalpha chain

Cortex, cortico-medullary junction, and the medulla

The three regions of the thymus in the order that T cells encounter them as they develop

Sufficient

The thymus is _______ for development

membrane bound

Unlike the surrogate light chain in the BCR, the surrogate alpha chain of the TCR is _____________

1) lymphoid progenitor seeds thymus 2) Cells commit to T cell lineage and become double negative (DN: CD4- and CD8-) 3) TCR rearranges and cells become double positive (DP: CD4+ and CD8+) 4) Positive and negative selection leads to single positive thymocytes (CD4+ OR CD8+)

What are the 4 stages of T cell development?

1) D-J rearranges first, then 2) V-DJ recombines 3) Finished TCRbeta chain pairs to surrogate alpha chain (pre-Talpha) and forms the pre-TCR 4) Pre-TCR stops beta chain rearrangement, starts alpha chain rearrangement (V-J recombination), drives proliferation, and induces expression of CD4 and CD8 co-receptors (becomes Double Positive) 5) Finished TCRalpha chain pairs with TCRbeta chain and goes to surface as TCR, stopping further alpha chain rearrangement 6) Down regulation to select for one of the co-receptors occurs (cell becomes single positive for CD4 OR CD8) 7) Exits thymus and enters the periphery

What are the steps of T Cell Development?

Expresses a single TCR specificity, recognizes self-MHC, and does not react strongly toward self-peptide antigens

What are the three requirements for T cell receptors?

Positive selection

What process determines which Co-receptor will be expressed on the surface of a T cell?

Bone marrow stem cells and thymus

What two things do T cells require for development?

FTOC (fetal thymic organ culture)

Where bone marrow stem cells are added to fetal thymi in vitro

TCRbeta

Which chain of the TCR is similar to the heavy chain of the BCR?

TRCalpha

Which chain of the TCR is similar to the light chain of the BCR?

alpha 1 and alpha 2

Which domains of the MHC I molecule have more variability in the gene encoding them?

alpha 1 and beta 2

Which domains of the MHC II molecule have more variability in the gene encoding them?

There is a greater recognition capacity than presentation capacity

Which is greater: TCR recognition capacity or peptide presentation capacity?

CD44 and CD25

adhesion molecules

CD25

inducable component of the IL-2 receptor

SCID mouse

mouse that has defective bone marrow stem cells

Nude mouse

mouse that has no thymus