Download presentation
Presentation is loading. Please wait.
1
Immunoglobulin Genetics
2
Immunoglobulin Genetics History
Same C region could associate with many V regions IgG Ab with different specificities Same V region could associate with many C regions Same idiotype on IgG and IgM Ab V and C regions coded for by separate genes
3
Light Chain Gene Families Germ line gene organization
J1 C1 E J2 C2 J3 C3 J4 C4 P L V1 Vn V2 Lambda light chain genes; n=30 P L V1 Vn V2 J2 J3 J5 C E J1 J4 Kappa light chain genes; n=300
4
Light Chain Gene Families Gene rearrangement and expression
V1 Vn V2 J2 J3 J5 C J1 J4 DNA P E P E L V1 J5 C V2 J4 DNA DNA Rearrangement E L V C J RNA Transcription Primary transcript C L V J RNA Processing RNA mRNA Protein Translation C L V J V C J Protein Transport to ER
5
Heavy Chain Gene Family Germ line gene organization
Introns separate exons coding for H chain domains Heavy chain genes; Vn=1000, Dn=15 P L V1 Vn V2 D2 D3 D1 Dn C C C3 C C 2 C 1 C 4 C1 C2 J2 J3 J5 J1 J4 E CH1 H CH2 CH3 CH4
6
Heavy Chain Gene Family Gene rearrangement and expression
Vn V2 D2 D3 D1 Dn C C J2 J3 J5 J1 J4 E DJ rearrangement P L Vn V1 V2 D2 D1 C C J5 J4 E DNA VDJ rearrangement D2 C C J5 J4 E P L V1 V2 DNA Transcription D2 C C J5 J4 E L V2 RNA Primary transcript
7
Heavy Chain Gene Family Gene rearrangement and expression
Primary transcript J4 D2 V2 C C J5 L RNA Processing An mRNA for C C L D J V C mRNA for C Translation C heavy chain C L D J V C C heavy chain Transport to ER C heavy chain V C C D J C C heavy chain
8
Mechanism of DNA Rearrangements
L V 2 J C 1 Lambda light chains Kappa light chains Heavy chains D Heptamer CACAGTG GTGTCAC Nonamer ACAAAAACC TGTTTTTGG 23 bp Two turn RSS GGTTTTTGT CCAAAAACA CACTGTG GTGACAC 12 bp One turn RSS Recombination signal sequences (RSS) Nonmer Heptamer 1 or 2 turn signals Rag-1 and Rag-2
9
Order of Ig Gene Expression
+ - Heavy chain gene VDJ recombination Productive rearrangement ? Yes No Transcribe/translate 1st 2nd or Apoptosis Progenitor B cell Pre B cell () Heavy chain Paternal Maternal
10
Order of Ig Gene Expression
+ - Light chain gene VJ recombination Productive rearrangement ? Yes No Transcribe/translate Light chain 4 th Apoptosis 1st - 2nd - 3rd - 4th - or Pre B cell Mature B cell +
11
Order of Ig Gene Expression Explains:
Why an individual B cell only produces one kind of Ig with one kind of heavy and one kind of light chain Why an individual B cell makes only makes antibodies of one specificity Why there is allelic exclusion
12
Origin of Antibody Diversity History
Definition - Diversity is the total of all the Ab specificities that an organism is capable of expressing Theories Germ line theory Somatic mutation theory
13
Origin of Antibody Diversity Current concepts
D region T G C Pro Trp V gene Pro Arg Pro Pro Multiple V genes V-J and V-D-J joining Junctional diversity N region insertions Amino acid sequences not encoded in the germ line
14
Generation of N region insertions
D J Break DNA J D TdT adds nucleotides -GTCAATG D J Ligate -GTCAATG- + D J N region insertion Intron
15
Origin of Antibody Diversity Current concepts
Multiple V genes V-J and V-D-J joining Junctional diversity N region insertions Somatic mutation Combinatorial association Multispecificity
16
Generation of Diversity
Ag independent process Clonal selection
17
T Cell Antigen Receptor
Heterodimer of an and a chain Gene structure and expression of the chain is analogous to the immunoglobulin heavy chain Gene structure and expression of the chain is analogous to the immunoglobulin light chain No somatic mutation in T cells
Similar presentations
