March 17th (Exam 3) Flashcards
How are T cell receptors and Immunoglobulins similar?
(three reasons, explain them)
- Similar structure - TCRs look like 1 of the fab arms of an immunoglobulin (both have a V and C region)
- Rearrangement - both rearrange genes to gain diversity in their variable regions
- Diversity/Specificity - both are diverse and specific only to one antigen
How are TCRs and Igs different in the type of antigens they recognize?
Igs recognize epitopes of intact molecules on the surface of a microbe
TCRs recognize peptides of antigen PLUS the MHC complex those peptides are bound to on the cellular surface
How are TCRs and Igs different in their secretion ability and adaptations of diversity after antigen binding?
Igs can be secreted and can undergo somatic hypermutation (CDRs) and isotype switching after antigen binding.
TCRs cannot be secreted and only exist in the membrane bound form and do not undergo any changes
What do these differences between Igs and TCRs tell us about their purposes?
They both recognize antigen, BUT
only Igs mediate effector functions.
What does the general structure of a TCR resemble?
a single fab arm of a IgG molecule
What are the two polypeptide chains that make up a TCR?
- alpha chain TCR(alpha)
- beta chain TCR(beta)
What are the distinct regions of each polypeptide in a TCR?
- V region
- C region
- Transmembrane region
- Cytoplasmic tail region
What are the distinct domains of each polypeptide in a TCR?
- Amino Terminal Domain
- C Domain
- Membrane anchoring Domain
What is the difference between a domain and a region?
A domain is the structurally unique section of the polypeptide whereas a region is a section which confers that part of the protein with specific functions.`
What forms the antigen recognition site in TCRs?
It is formed by the V(alpha) and V(beta) DOMAINS
Where is there the most variability among amino acids within the TCR?
(BE SPECIFIC)
The variability of the amino acids is concentrated within the hypervariable regions within the V region of both polypeptides.
How many CDRs are in EACH polypeptide?
3 in each.
Where are the genes that make up each polypeptide located?
TCR (alpha) chromosome 14
TCR (beta) chromosome 7
How would you compare the TCR (alpha) chain locus to that of the light chain locus of an Ig?
They both contain a variety of V and J segments that encode the variable domain
How would you compare the TCR (beta) chain locus to that of a heavy chain locus?
They both contain a variety of V, D, J segments that encode the variable domain.
How many varieties of Constant segments does the TCR (alpha) chain locus have?
The TCR (beta) chain locus?
Are there any functional differences between the constant segments of the beta chain?
alpha has one type
beta has two types but no functional difference
Analogous to immunoglobulins, where and when does rearrangement of T cell germline DNA happen?
In the thymus during T-cell development.
What flank the various gene segments and allow for recognition by RAG genes?
RSSs or Recombination Signal Sequences
What is the mechanism of gene rearrangement in B and T cells?
It is called V(D)J recombination
What does this rearrangement grant us?
V(D)J recombination results in clonal diversity of antigen receptors.
What is the name of the enzyme that is uniquely necessary for V(D)J recombination and therefore only made in lymphocytes?
RAG recombinase
V (D) J recombination is specific to…
Adaptive immunity
For what reason do RAG genes most likely not contain introns?
The reason, or hypothesis, is that RAG genes originated from transposons (by their nature they directly copy themselves and insert themselves into other places in the genome). They then evolved to encode the RAG proteins.
What must take place after the TCR alpha and beta loci have been rearranged respectively?
They must be transcribed,
Then spliced to have introns removed.
Then translation.
What distinct exons do each polypeptide of a TCR have?
- Leader Peptide
- V region (either VJ or VDJ)
- C region
- Membrane spanning region
Once the polypeptides have been translated, where do they go and what do they do?
They go to the ER and join to form alpha:beta TCR
How is alpha:beta TCR similar to immunoglobulin its limitations for association with the membrane?
They cannot leave the ER on their own and require help.
What is the help?
a combination of 4 types of invariant proteins that combine to form either homodimers (the zeta chain) or heterodimers (the CD3 complex).
What protein(s) make up the CD3 complex?
How are they arranged in relation to the alpha:beta TCR?
Where are the genes for these proteins located?
- CD3 epsilon (present in both heterodimers)
- CD3 gamma (present in one)
- CD3 delta (present in one)
Located all on chromosome 11
What protein(s) make up the zeta chain?
How are are they arranged?
Where are the genes for these protein(s) found?
just the zeta protein
They are a homodimer that associates with the alpha:beta TCR heterodimer
Chromosome 1
Once the CD3 heterodimers and the zeta homodimer have stabably associated with the alpha:beta TCR at the cell surface what do we call it?
The T-cell receptor complex
