The ppt covers the following topic-
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
2. SYNOPSIS
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA
rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
3. ANTIBODY
It is also known as antigen binding protein. ( made up of
glyocoprotein)
Produced by B-plasma cell.
Present on B- lymphocyte, memory cell as B-cell
receptor.
4. TYPES OF ANTIBODY
1) ISOTYPE They recognise same epitope but belong to
different classes.
2)IDIOTYPE They recognised different epitope.
3) ALLOTYPE They recognised same epitope.
5. GENETIC BASIS OF ANTIBODY DIVERSITY
Describe the genes that encode IG heavy & light chain.
Describe the sequence of IG gene rearrangment that
occurs during B-cell differentiation.
Discuss how diversity in antibody specificity is achieved.
Calculate the number of possible Igs which can be
produced from given no. of V,J,D & C genes.
6. ANTIBODY DIVERSITY
The generation of antibody diversity even in the absence
of antigen stimulation, a human can probably make more
than 1012 different antibody molecules its pre-immune
antibody repertoire.
Antibody consists of two heavy chains & two light chains.
Light chain have lamda and kappa constant region.
On the lamda region 22 chromosomes are present.
On the kappa region 2 chromosomes are present.
Heavy chain have 14 chromosomes.
It means AB forms by multi-genes.
During B-cell maturation these segments are rearranged
and brought together to form functional IG gene.
7. LIGHT CHAIN GENE SEGMENT
Each heavy chain and light chain gene contains
multiple copies of three different types of gene
segments for the variable regions of the AB
proteins.
The immunoglobulin lamda light chain locus
contains protein coding genes that can be lost with
its rearrangment.
V = variable region V1-V40.
J = join region J1-J5.
8.
9. MECHANISM OF VARIABLE REGION DNA
REARRANGMENT
Rearrangment occurs b/w specific sites on the DNA called RSS.
The signal sequence are composed of a conserved palidromic
heptamer & a conserved AT- rich nonamer.
V(D)J rearrangment with the help of V,J recombinase pairing
can be done
.
V(D)J recombinase encoded by gene RAG1 & RAG2.
To maintain the specificity of recombination, V(D)J recombinase
recognise & binds to RSS flanking the variable(v), diversity(d),
joining(j) segments.
10. RSS are composed of three elements
1) A heptamer of seven conserved nucleotides.
2) A spacer region of 12 or 23 basepairs in length.
3) A nonamer of nine conserved nucleotides.
In all variable segments this special RSS sequence
present behind the segments.
In all joining region RSS present in front segment.
Recombination is a random event in which RSS of V
region combines with RSS of J region.
11.
12. HEAVY CHAIN GENE SEGMENT
Heavy chain gene formed by four different segments
V =VARIABLE, D=DIVERSITY, J=JOIN, C= CONSTANT.
In human
Vh 51
Dh 27
Jh 6
Ch C𝜇, C𝛿, C𝛼, C𝛾, C𝜀.
In this DNA rearrangment occurs in two ways
In first step DJ recombination occurs then V to DJ
recombination by default the antibody is formed Igm then
Igd.
This process done at gene levels the class of IG is decided
by the alternative splicing.
13.
14. ALTERNATE SPLICING
Alternative splicing is regulated process during
gene expression that results in a single gene
coding for multiple protein.