antigen recognition Flashcards
how are antibodies made
b cells make antibodies, each cell can only make one type of antibody
once a specific b cell recognises matching antigen it undergoes clonal expansion so that its antibody may be released into the blood stream
what are principles of adaptive immunity
very specific receptors, can recognise differences at the single amino acid level. Diversity in enormous, huge amount of receptors in individuals (10^8-10)
describe basic antibody structure
variable heavy and variable light and constant heavy and constant light
part above the hinge is called Fab and part below is called Fc
light chain and heavy chain are not covalently bonded, mainly through hydrophobic interactions
describe dynamic of antigen-antibody binding
antibody antigen binding reaches an equilibrium:
antibody-antigen reactions are reversible (functionally irreversible, once an antigen binds it rarely unbinds, whole complex is usually destroyed)
equilibrium constant, K= [AbAg]/[Ab][Ag]
typical affinity of antibody/antigen binding is around 10^7-8/ mol (K=10^7-8)
how are diversity of antibodies generated
generation of diversity occurs during B cell development in the bone marrow
each B cell only has one specificity
wasteful process; many cells die
generates billions of possible sequences from less than 200 genes
(see biochem notes)
what loci are involved in antibody diversity
lamda light chain, kappa light chain, heavy chain
describe structure of heavy chain locus
V1-40, D1-27, J1-6, many constant regions which are irregularly named
what is antibody function
antibody acts as a receptor, binding of antigen leads to signalling to B cell to divide and differentiate leading to memory and antibody secretion.
IgA and IgB are the signal transduction molecules that cause the clonal expansion/ response to antigen binding
somatic hypermutation occurs, when antibody recognises antigen it mutates itself by single amino acids in order to try and achieve a higher affinity.
what is equivelant of antibodies on T cells, describe is structure
equivalent of antibody on T cells is called T cell receptor (TCR)
has 2 chains; alpha and beta, roughly the same size, each chain contains a constant domain and a variable domain
loops at end help determine specificity as in antibodies
generation of TCR diversity occurs in the same way as antibodies, in diversity beta is equivalent to heavy chain (since it has D regions) and alpha is equivalent to light (since there is not D region)
no somatic hypermutation
another population of TCRs which are TCRgammadelta which instead of having an alpha chain and a beta chain they have a gamma and a delta chain.
what are differences between TCRs and antibodies
in antibodies tight fit is needed between antibody and antigen and so conformation is crucial
TCRs instead of recognising whole 3D structure recognise a small linear peptide region of antigens in isolation
benefit of TCR recognition is that it is less susceptible to microbes becoming resistant by mutation of outer coat e.g flu mutation of outer coat
TCR can only recognise antigens that are bound to MHC
what are types and structure of MHC
2 classes; class 1 and class 2
MHC is made up of 3 domains; an alpha chain, beta2 microglobulin, and a peptide binding site, containing 2 alpha helices creating a V with a flat bottom composed of a beta sheet.
This cavity is used to bind proteins, when peptides bind to MHC they are deeply imbedded in the groove and barely visible to the T cell. When peptide binds to MHC it is bound and rarely leaves.
in humans there are 3 different class 1s and 3 different class2, class one is A,B and C and class 2 DR, DP and DQ
what do TCRs detect in the MHC-antigen complex
When TCRs detect MHC-antigen complex they are seeing a mixture of both self proteins (MHC) and foreign bodies (antigen peptide)
unlike antibodies/TCRs only 2 classes of MHC molecule which do not differentiate, MHC is able to detect large amount of antigens by having a relatively unspecific binding site, which detects peptides of a certain length.
what is ideal length of binding peptide for MHC
for class 1 ideal length of 9-10AAs
how does MHC bind antigens
For MHC class 1 ideal length of binding is a peptide with 9-10AAs, binds to peptide backbone not R groups allowing for less specificity
since peptides have amino acid R groups facing opposite directions due to steric factors creates higher specificity of binding due to beta sheet at bottom of peptide binding site. peptides it can bind are limited to ones with long or hydrophobic groups at specific points in the structure.
Side chains determine whether MHC can bind, side chains pointing out of MHC-antigen complex is what T cell is exposed to and so determines binding of TRC
what types of cells do MHC interact with
Class 1 MHC interacts with CD8 cells
Class 2 MHC interacts with CD4 cells
class 1 pathway of antigen processing is called endogenous pathway, class 2 is exogenous pathway
what are differences in MHC
MHC molecule is polymorphic (slight differences between people), doesnt affect an individuals ability to present an antigen, however peptides which are present in a population differ, which means it is hard for viruses to mutate specifically.
what is involved in exogenous antigen processing
exogenous antigen processing: peptides which bind to MHC2 are derived from antigens taken up from external environment e.g loose antigens due to phagocytosis of bacteria
antigen is taken up by antigen presenting cells or dendritic cells via endocytosis, in the endosome it is degraded
MHC is a glycoprotein and so is produced in the endoplasmic reticulum, vesicles containing MHC and antigen peptide fragments fuse and are taken to surface where MHC-peptide complex is presented and is target for CD4 cells.
in what state is MHC during non infectious periods
Before MHC vesicle binds to peptide vesicle MHC is bound to invariant chain which prevents it from binding other peptides
Even when pathogens are not present this process is continuous, meaning most MHC in your body is bound to self proteins taken up such as serum proteins or membrane proteins, however T cells know not to respond to these self proteins
this process only occurs in exogenous pathway, and so only applies to MHC class 2
describe the endogenous pathway
MHC still made in endoplasmic reticulum
no invariant chain since peptides are added to MHC in the endoplasmic reticulum
antigens/proteins are degraded by proteasome which degrades it into peptides.
Peptides in the cell are transported into the ER by transporter antigen protein (TAP) where they bind MHC.
exogenous pathway target proteins outside of cell e.g bacteria
endogenous pathway targets proteins inside cell e.g viruses
how is signal transduced when antigen binds to TCR
signal transducers for TCRs are accessory molecules called the CD3 complex which are associated with the TCR.
how might viruses evade antigen recognition
viruses have evolved mechanisms to avoid immune recognition via endogenous pathway.
