lecture 3- antigen recognition Flashcards
What is the structure of an immunoglobulin monomer?
H2L2= 2 identical heavy chains disulfide bonded to two identical light chains
TCRs and BCRs are also known as____ or ____
Immunoglobulins or antibodies
The amino end of the H and L chain has the ____ region, the C terminal has the ____ region
variable region
constant region
So then, where are the regions in the Ig that interact with the antigen?!
In the variable region, there are three regions of hypervariability called the complementarity determining regions CDR1, CDR2, CDR3
With all this function of the variable region of Ig, what does the constant region even do?
The constant region of the H chain determines the isotype of the Ig. Note that there are 9 isotypes and 5 classes of Ig. Ig classes: IgA, IgM, IgD, IgE, IgG
Are Ig’s monomers?
Yes, Igs are monomers. BUT in the soluble form only IGD, IgE, IgG are monomers and IgA is a dimer and IgM is a pentamer held together by a j chain
What is Fc and Fab?
Fc is in the c terminal and modulated effector functions (recruit immune response) when Fab which is in the variable domain is bound to by antigen
whats the structure of TCR?
The TCR is a hetero-dimer, comprised of a TCR alpha chain and a TCR Beta chain. Like Ig there is amino-terminal variable region and a carboxylterminal constant region that traverses the T cell membrane. The variable region has CDR1, CDR2 and CDR3 hypervariable regions.
(5%-10%) express a γδ TCR chain, instead of an αβ TCR
whats the difference between an epitope and an antigen
an epitope is the part of the antigen that actually binds to the antigen receptor.
how are TCRs and BCRs different functionally?
TCRs don’t recognize the whole antigen, they recognize peptides in the antigen presented to the TCR by an MHC. CDR1&2 contact the MHC while CDR3 connect with the peptide
BCRs can recognize a variety of chemical features
Who expresses MHC1 vs MHC2
MHC1 expressed by normal nucleated cells
MHC2 expressed by Antigen presenting Cells (APCs) like dendritic cells, B cells and macrophages. *note that thymic epithelial cells also present MHC2.
what is the difference between MHC1 and MHC2 structurally
MHC1 is comprised of an alpha chain with 3 domains and a beta chain of one domain. MHC2 is a heterodimer of an alpha chain and beta chain of two domains each. The peptide binding cleft in 1 is just a fold between two domains of alpha chain, in 2 it is made of the alpha and beta chain.
MHCs are also known as ____ in humans
HLA
What 3 HLA loci make MHC1?
MHC2?
A,B,C
DP, DQ, DR
part of the antigen peptide that contacts the MHC is called_______, the part that contacts the Tcell is called_____
(1) anchor residue
(2) TCR contact residue
what causes the high degree of MHC polymorhphism?
A person inherits 3 alleles of MHC1 and 2 each. The alleles are codominant so each person can produce 6 classes of MHC1 molecules and 12 classes of MHC2 molecules.
pros and cons of MHC polymorphism?
pro- makes it more likely that an individual is able to present an antigen, makes it more likely that someone in the population will be able to do so
cons- organ transplant rejection
What are CD4 and CD8 and how do they differ?
They are coreceptors on a Tcell. They help increase the avidity of TCR to the peptide by binding the MHC that is presenting the peptide.
CD4======= MHC2, extracellular antigen CD8======= MHC1, intracellular antigen
describe the MHC1 presentation pathway.
An intracellular peptide is digested by a proteasome into small pieces. These pieces enter the ER via TAP and bind to newly synthesized MHC1. Then they are exocytosed and presented on the cell surface
describe the MHC2 presentation pathway
The extracellular peptide is phagocytosed/endocytosed. The phagosome fuses with a lysosome and the peptide is degraded to smaller pieces. The newly synthesized MHC2 proteins have their peptide cleft blocked by Ii (invariant chain) leaves the ER and fuses with the lysosome and Ii is degraded allowing the peptide to bind.
what is the path by which T-cells with CD4 receptors conduct an immune response
CD4 receptors bind to MHC2, which presents extracellular peptide to the Tcell. Tcells with CD4 are called Helper T cells. They can (1) secrete cytokine to activate macrophage killing of the cell (2) secrete cytokine when the APC is a B-cell to activate antibody production by B cell
what is the path by which T-cells with CD8 receptors conduct an immune response
CD8 receptors bind to MHC1, which presents intracellular pathogen peptide to T cell. Tcell with CD8 are Killer T Cells and binding to MHC1 activated them to directly kill the cell (which is the source of infection!)
