Thymus-Derived Cells (T Cells) Flashcards
What is the lifespan of a T cell?
6 months to over 20 years.
T cells constitute up to ___ of the recirculating pool of small lymphocytes.
80%
What do developing T cells acquire in the thymus?
Antigen-specific receptors and other functional and phenotypic characteristics that mark it as a mature T cell.
What are the functions of mature T cells’ surface proteins?
Antigen recognition, signal transduction, and adhesion to APCs + target cells.
Activation of a cell surface receptor requires binding to its specific ____, which may be a ____-_____ on another cell or soluble protein.
ligand; counter-receptor.
What are some of the accessory molecules’ functions on T cells?
- Adhesion molecules.
- Deliver signals to the T cell that functions, in concert with signals from the TCR-CD3/zz complex, to fully activate the T cell.
Generally speaking, what do CD4 and CD8 molecules do?
They promote the adhesion of T cells to APCs and target cells and also play a role in signal transduction, thereby potentiating T cell activation.
Where is CD4 (TCR co-receptor) found?
On helper T cells [present on monocytes and macrophages of some species].
What does CD4 bind to?
It binds to the B2 domain of the class 2 MHC molecules on the surface of professional APCs.
Where is CD8 (TCR co-receptor) found?
On cytotoxic T cells.
What does CD8 bind to and what is its function?
Its function is the recognition of the a3 domain of class 1 MHC molecules, enabling cytotoxic T cells to bind to target cells.
Generally speaking, what is the function of lymphocyte adherence molecules?
They strengthen interactions between helper T cells and professional APCs or cytotoxic T cells and target cells (e.g., virus-infected cells).
What is CD11aCD18? What does it bind to? What is its function?
It is lymphocyte function-associated antigen-1, LFA-1); it binds T cells to CD54 molecules (ICAM-1,2,3) on APCs and target cells; it promotes the binding of T cells to endothelial cells during T cell extravasation.
What is CD2? Where is it found? What does it bind to? What is its function?
CD2 is LFA-2; CD2 molecules are found on mature T cells; CD2 binds to a protein called CD58 (LFA-3) present on APCs and target cells; CD2 functions both as an intracellular adhesion molecule and as a T cell signal transducer [contributes to optimal T cell activation].
What is CD28? Where is it expressed? What are its ligands? Where are these ligands expressed?
- CD28 is a constitutively expressed membrane receptor for co-stimulatory signals (signal 2).
- Its ligands are B7-1 (CD80) and B7-2 (CD86) cell surface proteins that are expressed on professional APCs.
- NOTE: IL-6 and IL-1 can help function as B7 proteins if you do not have any B-7s, but they are not as potent.
What does signal 2 function with? What do these two signals do?
- Signal 2 functions with signal 1 (delivered by the TCR complex) to activate naive T cells.
- Signal 2 is when the T cell is exposed to co-stimulating molecules such as cytokines and cell membrane proteins produced by the APC.
What does the TCR complex consist of?
- T cell receptor (TCR).
- CD3 Complex.
- z (zeta) proteins.
What kind of protein is the TCR?
A disulfide-linked heterodimer glycoprotein.
What does the TCR enable T cells to do?
The TCR enables T cells to recognize processed antigens presented in association with MHC molecules.
What are the two identified types of TCRs?
TCRaB and TCRgd
Explain the construction of TCRaB.
The aB chains are integral membrane proteins with an extracellular domain, a transmembrane domain, and a short cytoplasmic tail. The extracellular domains consist of variable (N-terminal), constant and hinge regions.
What are hyper-variable regions?
- Complementarity-determining regions (CDRs), which reside in the variable regions; they consist of unique amino acid sequences that form the antigen-binding site of the TCR.
- BOTH CHAINS POSSESS 3 CDRs (1,2,3) JUXTAPOSED TO ONE ANOTHER.
Where is CDR3 located? How diverse is it? And what does it interact with?
CDR3 is located in the center of the CDRs; it displays the most diversity; and directly interacts with the antigenic peptide.
What does CDR1 interact with?
CDR1 interacts with both peptide and the MHC.
What does CDR2 interact with?
CDR2 interacts with the MHC.
What part of the TCRaB contains a 4th hyper-variable region? What does this 4th region do?
The B-chain and the V-domain contains a 4th hyper-variable region, which is the binding site for microbial products called superantigens.
How many TCRs does a single T cell possess?
About 50,000.
Each TCR is ______, ie, will recognize only a single epitope bound to an MHC protein.
Clonotypic.
In humans and nonruminants, ____-____% of T cells carry aB receptors.
90-99%.
T or F?
TCR is produced in secreted form, and therefore performs effector functions on its own.
FALSE.
Unlike BCR, TCR is not produced in secreted form, hence it does not perform effector functions on its own.
T or F?
TCRs can respond to as many different foregin antigens as possible, but not to self-antigens.
TRUE.
What controls the genetic expression of TCRs?
Allelic exclusion. It occurs when only one of the parental alleles that code for the TCR is functional, rendering each T cell responsive to only a single epitope.
T or F?
The genes encoding the a chain and B chain are found on the same chromosome.
FALSE.
The genes encoding the a-chain and B chain are found on SEPARATE chromosomes.
What regulates the rearrangement of TCR gene segments and BCR gene segments?
Several enzymes collectively called recombinases.
What are RAG-1 and RAG-2? Where are they found? Where are they active?
RAG-1 and RAG-2 are recombination-activating genes 1 and 2. They are only found on T and B lymphocytes; however, they are active only in developing lymphocytes.
TCR and BCR rearrangements DO NOT continue in mature T and B cells that have completed gene rearrangements… why?
Because RAG-1 and RAG-2 are only active in developing lymphocytes.
What do RAG proteins cleave?
DNA at recombination sequences which are located adjacent to the V, D, or J coding sequence.
T or F?
Individuals or animals lacking RAG genes fail to produce both BCR and TCR proteins and manifest severe combined immunodeficiency, SCID.
TRUE.
T or F?
Like RAG proteins, DNA repair enzymes are expressed in only a few cell types.
FALSE.
UNLIKE RAG proteins, DNA repair enzymes are expressed in MANY cell types.
What is DNA repair enzymes role in TCR and immunoglobulin (BCR) gene recombination?
To repair the double-stranded breaks introduced by the RAG proteins.
T or F?
Lacking DNA repair enzymes will also result in SCID.
TRUE.
What is the purpose of TCR gene rearrangements?
Deletion of unwanted genes.
Describe the two general steps of TCR gene rearrangements.
1) Cells initially loop out unwanted genes and then excise them.
2) The cut ends are joined by DNA ligase.
What is the first chain genes of the TCR that rearranges before the others?
The B chain genes, followed by the a chain genes.
What are the three region genes that occur at the TCRB locus?
- Multiple variable (Vn) region genes.
- Diversity (Dn) region genes.
- Joining (Jn) region genes.
What are the three steps of the B chain gene rearrangement?
First, DB gene segments rearrange and join to JB gene segments, followed by VB to the DJB gene rearrangement, and then to a CB gene.
Where are the multiple variable (Vn) region genes and joining (Jn) region genes occur at in a-chain gene rearrangement?
At the TCRa locus.
T or F?
During the rearrangement of a-chain genes, a randomly selected V gene is jointed to a J gene and the exon is transcribed, combined with a constant (Ca) regeion gene, and translated.
True.
What does multiple germ-line genes; gene rearrangements; and junctional diversity account for?
The diversity of TCRaB.
Removal of a few bases from the broken ends of the coding sequences by endonucleases is called…?
Base deletions.
How does base deletions affect diversity in the TCRaB?
Base deletions will affect the which precise nucleotide at which V, D, and J genes can join, resulting in greater diversity.
What does the enzyme terminal deoxynucleotidyl transferase (TdT) do?
It adds up to 10 nucleotides to the cut ends of the V/J (a-chain) and V/D/J (B-chain) coding sequences in a process called N-REGION NUCLEOTIDE ADDITION.
What are P-nucleotides?
When a gene is cleaved asymmetrically, the shorter strand is usually extended with nucleotides complementary to the longer strand before the two are ligated. The added nucleotides at the V/D/J and V/J sections are called P-nucleotides.
