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1. Introduction
2. The plague of Athens
3. Smallpox inoculation
4. The first vaccination
5. Protection from infection by infected serum
6. Questions regarding antibodies
7. Side-chain theory (Ehrlich, 1900)
8. Clonal selection theory (Burnet, 1957) (1)
9. The structure of antibodies
10. The structure of immunoglobulins
11. Antibody variable region sequence
12. Structure of light-chain C and V domain
13. Ag-binding site formed by beta-strands loops
14. Three dimensional structure of variable region
15. Classification of antibodies
16. Generating diverse antibody specifities
17. Clonal selection theory (Burnet, 1957) (2)
18. Germline and somatic mutation theories
19. The Ab N-terminal domain contributes to diversity
20. Different hypothesis regarding antibody diversity
21. Gene rearrangement
22. Rearrangement in light and heavy chains (1)
23. Rearrangement in light and heavy chains (2)
24. Functional gene segment on human Ig loci
25. Molecular mechanism of gene rearrangement
26. RAG - rearrangement activating gene
27. 12/23 rule restricts V(D)J recombination
28. Rearrangement of IgH loci during development
29. RAG locus
30. V(D)J recombination
31. Initiation of V(D)J recombination
32. TdT contributes to Ab diversity
33. Junctional sequences of IgH rearrangements
34. Dynamics of V(D)J recombination
35. Other diversities in antibody structure
36. Repertoire of functional antibodies
37. B cells must have an antigen surface receptor
38. Ab secreted form and Ab receptor form
39. Membrane-bound IgM
40. Transmembranal IgM versus secreted IgM
41. High affinity Ab depends on somatic mutation
42. From IgM to IgG - class switch
43. Somatic hypermutation
44. Somatic mutation of immunoglobulin genes
45. Hypothesis regarding Ab diversity
46. Immunoglobulin gene conversion
47. Birds and rabbits use gene conversion
48. Class switch determines Ab response
49. Changing the Ab isotpe
50. Class switch recombination
51. Functional Ab genes
52. What is AID and how does it works?
53. Three distinct processes
54. AID determination
55. DNA lesions and their source
56. AID generates a UG lesion
57. Uracil DNA glycosylase
58. AID deamination
59. Evidence for DNA deamination mechanism (1)
60. AID can mutate bacteria
61. AID deaminates ssDNA oligonucleotide in vitro
62. Evidence for DNA deamination mechanism (2)
63. Mutations in Ab gene diversity program
64. UNG/MSH2 deficiencies block class switch (1)
65. UNG/MSH2 deficiencies block class switch (2)
66. AID deamination - conclusion
67. Mistargeted gene rearrangements and cancer
68. Generation of antibody diversity
69. AID ancestors
70. Other AID related proteins
71. Comparing AID and dCMP DA
72. APOBEC1 is involved in RNA editing
73. APOBEC1 in apolipoprotein production
74. APOBEC2 is as old as AID
75. The evolution of AID and APOBEC proteins
76. AID versus APOBEC3
77. RIP - repeat-induced point mutation
78. dC deamination and dC methylation
79. Conclusion

Topics Covered

• Historical perspective on antibodies and immunity
• Nature and structure of antibodies and immunoglobulin fold
• Theories of antibody formation
• Clonal selection theory
• Mechanisms contributing to antibody diversity
• Organization of immunoglobulin loci
• Immunoglobulin gene rearrangement and generation of the primary repertoire
• RSS elements
• RAG genes and mechanism of V-D-J joining
• Membrane immunoglobulin and the B-cell antigen receptor
• Secondary antibody repertoire and diversification of rearranged immunoglobulin genes
• Affinity maturation
• Somatic hypermutation, gene conversion and class-switch recombination
• DNA deamination as a central trigger for these three diversification processes
• Detailed pathways of antibody gene diversification
• AID and the evolution of DNA deamination

Links

Series:

• Monoclonal Antibodies as Therapeutic Agents

Categories:

• Immunology

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Publication History

• Published on October 1, 2007

Financial Disclosures

• Prof. Michael Neuberger has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.