T-Cell Development Flashcards
Where do T cell precursors migrate?
To the thymus
What generates a naive T cell with a unique TCR?
Somatic recombination in the thymus
How is an alpha chain formed?
Recombinase rearranges V and J gene segments to form an alpha chain
What happens if the recombination reaction is productive and why?
Recombinase is shut off at the other alpha chain locus to prevent individual cells from expressing more than one TCR
What is the structure of a TCR like?
A heterodimer composed of an alpha and beta chain
Each chain contains a V and C region
What region on a TCR recognizes antigens?
The V region
What are some similarities between TCRs and Ig molecules?
Both are composed of two chains that combine to form variable and constant regions
Both have flexible hinge regions
What is the difference between TCRs and Ig molecules?
The TCR is directly and permanently anchored in the plasma membrane and thus the C-terminus has no effector functions and is needed for signaling
What do CD4 and CD8 interact with?
Non-polymorphic residues in MCH class 1 and 2, not the antigenic peptide
What are the forms of antigens recognized by TCRs?
Peptides displayed by MHC molecules on APCs
Linear epitopes
What is the diversity of TCRs?
Each clone has a unique specificity
What is antigen recognition mediated by in TCRs?
Variable regions of the alpha and beta chains
What are the signaling functions mediated by in TCRs?
Proteins associated with TCR
How does TCR develop in the thymus?
Thymic epithelial cells presents self antigen on MCH 1 and 2
What are self-antigens?
A collection of thymus and non-thymus peptides
What is positive selection?
When the TCR-MHC interaction determines they type of T cell it will be
If a TCR recognizes an MHC 2 molecule, what happens?
The cell loses the CD8 expression and becomes a CD4 T cell
What happens if the TCR recognizes no MHC?
Failure of positive selection/death by neglect
Non-reactive T cell is removed from the thymus through apoptosis
What is negative selection?
When auto-reactive, high affinity self recognizing TCR expressing T cells are removed from the thymus through apoptosis
What does positive and negative selection generate?
A pool of CD4 and CD8 lymphocytes with low affinity for self peptide-self MHC complexes
What does positive and negative selection ensure?
Positive = ensures MHC restriction
Negative = ensure binding affinity
What are CD4 and CD8 T cells restricted to?
CD4 = MHC 2/peptide
CD8 = MHC 1/peptide
Where does positive selection occur?
In the cortex of the thymus
Where does negative selection occur?
In the medulla of the thymus
Why do naive CD4 and CD8 T cells migrate to peripheral lymphoid organs?
To look for antigen on MHC class 1 or 2
