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antibody structure and diversity, T cell reseptor diversity - Coggle…
antibody structure and diversity
structure
4 polypeptides
2 heavy chain
2 light chain
to main classes
kappa
human 2/3 of antibody has this
lambda
y shape
include flexible hinge region
2 antigen binding cites
one is formed form 1 heavy chain and 1 light chain
formed from v domain
variable reagion
Vh
VL
a lot of variability in amino acid sequence
constant region
ch
diffrenese in ch define 5 main isotypes
Igg
a segment can be cleaved with protease
fab X2
#
fc
Igm
igd
iga
ige
cl
limited sequence variation
imunoglobulin domain
v domain (variable domain)
constant domains
1 domain In light chain
3-4 in heavy chain
tow batea sheets held together with a hydrophobic interaction
disulfide bond
antigen binding
hyperverible region
diffrences in amino acid sequins in have and light chain region are consecrated in these
hype reversible regions flanked by framework regions
3 loops per vh and vl
placed at loppes farthest from c region
also known as complementary determining region
together 6 cdrs per binding site
how and how many of them in contact with antigen based on size shape + chemical properties
localised varibilety
determine spesefisety at antigen binging site
can agomedate multiple different epitopes
complementary interacting surface complementing epitope
antigen bind to outside surface of pathogen
antigenic determinant/ epitope
part of antigen that antibody binds
complexe macromolecule many epitopes
multivalent antigen
linear epitope
formed by eccsesseble loops in proton ateigen
discontinues epitopes
2+ part of the protein antigen that are separate in amino acids sequins but come tigethe in 3 dimensional structure
non kovalent reveseble interactions
hydrogen bonds
wander wall interaction
bindig site ritch in aromatic amino acid
electrostaic interaction
hydrophobic interactions
difference in affinity
antibody cues for reserch
clinical trials
at home test (covid 19)
made by immunising animals with antigen
preparing aster from blood
asteria qualeti depends on blood purety
poly clonal antiserum
other way of making
monoclonal antibodies
reaction with types of cell measured with flow cytrometry
stream of celles passes trong laser
celles cause laser to emit light of different wayvelanght
abundance of cell surface molecule measured
useful to treat mant human dessises
rituximab
bind to b cell cd20
by nk cell
complete fiction leading to macrophage mediated phagocytosis
alemtuzumab
target cd52 og b and t cell on monocytes and eosynpphils
marge tuximab
evenacumab
target angiopoitin
increase in leases that decreases ldl
fremanezumab
bind to cgrp
cgrp cause neurodamic inflammation
first monoclonal antibody from mice was human made antibody agents the foren antybody
made chimeric antibodes
mouse constant region replaced with human constant region
humanised antibodies
mice immunising mice with human immunoglobulins gene
only part of mouse antibody left is Cdr loops
mice immunised with antigen
b celle taken from sullen og lyph nodes
then fused with imortolaised b cell tumor
tumor with no functional immunoglobulin genes
hybrid celles
imortal and can only produce 1 antibody
monocoal antibody
grown in culture
T cell reseptor diversity
T cell receptor structure
receble fab fragment
2 polypeptide chains
moste of them
1 alpha chain
1 beta chain
gene coding for chains need rearrangement to form functioning gene
like immunoglobulin genes
both chains has a v and c region
hyperverible region
lopps in polypeptide fardest from T cell membrane
form antigen binding cite
only one
#
cdr1, cd2 , cdr 3
high amino acid sequence variation
most humans have many milion different T cell receptors
domains
amino terminal v domain
c domain
membrane ancorino domain
antigen recognition done by va and vb domanin
gene rearangement
locus receptor a chain chromosome 14
1 ca gene
similar to immunoglobullin light chain locus
arrays of v and j gene segments
for alpha chain a va and ja segments creates functional exon
somatic recombination
locus receptor b chain chromosome 7
2 cb gene but no known difference
similar to immunoglobulin havychain locus
arrays og d gene segments + v and j segments
for beta chain vb jb and db segments create a functioning exon
first rearrangement of d and j = dj segment
second v rearengment to dj segment= vdj segment
simerarety with immunoglobulin in gene segment organisation
happens in thymus
gen segments flancked by rss-s
Rag
involved in cutting and splicing of gene segments
n and p nucleotides
inserted between vdj segments during rearrangement
causes most diversity in cd3s of both chains
after rearengmet
primers rna is spiled to remove introns
when newly synthesised (both Chains)
enter the ER
pairs up and forms alfa beta receptor