Antibody diversity

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.

1. EVOLUTION OF ANTIBODY DIVERSITY

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 10 12 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. 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.

9. 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.

10. 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  C , C , C , C , C . 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.  

11. ALTERNATE SPLICING Alternative splicing is regulated process during gene expression that results in a single gene coding for multiple protein.