Lecture 9 Flashcards
Differences between TCR and BCR
-only 1 antigen binding site—>monovalent
-always membrane bound (cannot be secreted)
-1 type of constant region–>NO istotypes/switching
-binds to antigen as a complex with a MHC molecule
-lower affinity for antigen than antibody
What 2 distinct types of TCRs are generated?
-alpha & beta T cell (more abundant)
-gamma & delta (more rare)
True or false: A T cell can express more than 1 TCR
False
-T cell will express only 1 TCR
-NO coexpression of alpha beta and gamma delta TCR
-1 at a time
What are the mechanisms for diversity for T cells?
Before Antigen stimulation
1. Somatic recombination
2. Imprecise junction
3. Combinatorial Pairing
True or false: Somatic hypermutation occurs in T cell development
False
-no somatic hypermutation, NO isotype switching, NO AID–>somatic hypermutation allows for antibody diversity–>T cells do not secrete antibodies, instead gets diversity in thymus
-there is NO change AFTER antigen stimulation
Does the alpha chain locus have a D segment
No D segment–>only V and J
-similar to light chain of immunoglobulin locus
Does the beta chain locus have a D segment?
Yes it has a D segment–>V, D and J segments
What happens if someone does not have a RAG protein?
If no RAG protein then No B cells or T cells can be made since RAG is used in rearrangement for both types of cells
What is severe combined immuno deficiency (SCID) syndrome?
When you lack B-cells and T-cells b/c no RAG
-get bone marrow transplant as treatment to re introduce RAG proteins
In the Gamma/delta gene segments where is the delta segment?
In between the V & J segments of variable alpha chain
-once T cell recombines it deletes the delta segment
What is CD3 polypeptide chains and z chain used for?
The transport of newly synthesized TCR to the cell surface and for the transduction of signals to the cell interior after TCR binds to specific MCH-Ag
-TCR never goes to surface if no CD3
-Once TCR is bound to antigen allows for signaling–>activates clonal expansion differentiation
How does CD4 and CD8 coreceptors help MHC binding?
They bind to the MHC membrane proximal region and stabilize the TCR and MHC peptide binding
What does CD8 bind to and make ?
Alpha3 domain of MHC I–>Cytotoxic T lymphocyte (CTL)
What does CD4 bind to and make?
Beta2 domain of MHC II–>Helper T lymphocyte (Th)
What does it mean for a gene to be allelic?
Variant of genes
-alternate forms/variants of genes
-Ex: blood type
What does it mean for a gene to be monomorphic?
Only 1 version of a gene–>is the same for everyone
-Ex: RAG protein
What does it mean for a gene to be polymorphic?
Multiple alleles exist in the population that can be inherited
What is a homozygote?
Sets of chromosomes are the same
What is a heterozygote?
Alleles are different
What does it mean to be polygenetic?
Different types of genes of MHC I and MHC II
-Ex: MHC I–>HLA-A,HLA-B,HLA-C
What does it mean to be polymorphic?
There are alternative forms of each MHC type (alleles) within a population–>variations of alleles
-Ex: HLA-A, HLA-A1, HLA-A2
What is known as the most polymorphic genes?
MHC genes
-specifically MHC I
What is MHC known as?
Human Leukocyte Antigens (HLA)
What is a haplotype?
A combination of alleles on the same chromosome
What kind of inheritence is expressed for MHC
Co-dominant
-both alleles for each MHC gene type are expressed
What contributes to the diversity of MHC molecules expressed by an individual?
Polymorphism and polygeny
What 3 important things does MHC complex control?
- MHC recognition–>T cell recognition of antigen
- Immune response (Ir) genes (selectively respond to antigen)
- Graft rejection (reject organ grafts)
Explain MHC restriction
T cell recognition can only happen if the correct MHC allele & antigen are bound
-if 1 of them is incorrect there is no recognition
Syngeneic
Genetically identical due to inbreeding
-No polymorphism
-same MHC alleles/haplotype
Allogenic
Genetically disparate (wild mice)
-different MHC alleles/haplotypes
Congenic
Genetically identical w/ exception of 1 genetic locus
-made by backcrossing & selection
-congenic mice are homozygous for a and b haplotype
True or false: Immune response (Ir) genes map to the MHC
True
True or false: MHC peptide binding is promiscuous (one type of peptide) NOT highly specific
True
How does graft rejection work?
-T cells that recognize self antigens (MHCs) with high affinity are eliminated through the process of negative selection graft is ACCEPTED
-T cells that are non self (foreign) are NOT deleted graft is REJECTED–>T lymphocytes use cytotoxic T cells to kill skin cells
T cell receptors structurally resemble?
Fab of immunoglobulins
