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- Improving on "Natural" Rodent Antibodies
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1. The immunogenicity problem in antibody therapy
- Prof. Herman Waldmann
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2. Antibodies by protein engineering
- Prof. Sir Gregory Winter
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3. The generation of diversity in antibody genes
- Prof. Michael Neuberger
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4. Innate immunity to retroelements by human AID/APOBEC3 proteins
- Prof. Reuben Harris
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5. Fc receptors and antibody effector functions
- Dr. Mike Clark
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6. Antibody engineering of Fc effector functions
- Dr. Mike Clark
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7. Antibody engineering: beginnings to bispecifics and beyond
- Dr. Ian Wilkinson
- Antibodies in Cancer Therapy
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8. Monoclonal antibodies and the ErbB system in human cancer
- Prof. Mark Greene
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9. Checkpoint blockade in cancer immunotherapy
- Prof. James Allison
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10. Monoclonal antibodies in haemato-oncology
- Prof. Mark Cragg
- Diagnostic Antibodies
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11. Monitoring therapy with antibodies
- Dr. Geoffrey Hale
- Cell Surface Glycoproteins on Cells of the Immune System
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12. Cell surface glycoproteins on cells of the immune system
- Prof. Neil Barclay
- Antibodies as Immunosuppressants
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13. Monoclonal antibodies to induce therapeutic immunological tolerance
- Prof. Herman Waldmann
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14. Antibodies to control or prevent type 1 diabetes
- Dr. Robert Hilbrands
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15. Antibody therapy of multiple sclerosis
- Dr. Alasdair Coles
- Prof. Alastair Compston
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16. Monoclonal antibodies in the management of rheumatoid arthritis
- Prof. John Isaacs
- Archived Lectures *These may not cover the latest advances in the field
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19. Alemtuzumab (Campath-1H) in therapy of CLL
- Prof. Kanti Rai
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20. VEGF inhibitors for anti-angiogenic therapy
- Prof. Kari Alitalo
- Dr. Bronislaw Pytowski
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21. Human antibodies produced in mice
- Dr. Marianne Bruggemann
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22. New strategies to prevent transplant rejection: from molecules to mice to monkeys to man
- Prof. Christian Larsen
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23. CD20 antibodies in the targeting of B-cell malignancies and autoimmunity
- Prof. Thomas Tedder
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24. Anti-IL-2 receptor antibodies as models for cancer therapy
- Prof. Thomas Waldmann
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25. Anti TNF therapy in rheumatoid arthritis
- Prof. Marc Feldmann
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26. Novel immunotherapeutic proteins: immunoligand
- Prof. Terry Strom
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27. Diagnostic immunohistopathology
- Prof. David Mason
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28. Antibodies in the control of type I diabetes
- Prof. Lucienne Chatenoud
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29. The challenge of targeting toxins to tumors
- Prof. Ben Seon
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30. Antibody depletion therapy in transplantation: implications for tolerance
- Prof. Laurence Turka
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31. Antibodies as anti-virals
- Prof. Dennis Burton
Printable Handouts
Navigable Slide Index
- Introduction
- The plague of Athens
- Smallpox inoculation
- The first vaccination
- Protection from infection by infected serum
- Questions regarding antibodies
- Side-chain theory (Ehrlich, 1900)
- Clonal selection theory (Burnet, 1957) (1)
- The structure of antibodies
- The structure of immunoglobulins
- Antibody variable region sequence
- Structure of light-chain C and V domain
- Ag-binding site formed by beta-strands loops
- Three dimensional structure of variable region
- Classification of antibodies
- Generating diverse antibody specifities
- Clonal selection theory (Burnet, 1957) (2)
- Germline and somatic mutation theories
- The Ab N-terminal domain contributes to diversity
- Different hypothesis regarding antibody diversity
- Gene rearrangement
- Rearrangement in light and heavy chains (1)
- Rearrangement in light and heavy chains (2)
- Functional gene segment on human Ig loci
- Molecular mechanism of gene rearrangement
- RAG - rearrangement activating gene
- 12/23 rule restricts V(D)J recombination
- Rearrangement of IgH loci during development
- RAG locus
- V(D)J recombination
- Initiation of V(D)J recombination
- TdT contributes to Ab diversity
- Junctional sequences of IgH rearrangements
- Dynamics of V(D)J recombination
- Other diversities in antibody structure
- Repertoire of functional antibodies
- B cells must have an antigen surface receptor
- Ab secreted form and Ab receptor form
- Membrane-bound IgM
- Transmembranal IgM versus secreted IgM
- High affinity Ab depends on somatic mutation
- From IgM to IgG - class switch
- Somatic hypermutation
- Somatic mutation of immunoglobulin genes
- Hypothesis regarding Ab diversity
- Immunoglobulin gene conversion
- Birds and rabbits use gene conversion
- Class switch determines Ab response
- Changing the Ab isotpe
- Class switch recombination
- Functional Ab genes
- What is AID and how does it works?
- Three distinct processes
- AID determination
- DNA lesions and their source
- AID generates a UG lesion
- Uracil DNA glycosylase
- AID deamination
- Evidence for DNA deamination mechanism (1)
- AID can mutate bacteria
- AID deaminates ssDNA oligonucleotide in vitro
- Evidence for DNA deamination mechanism (2)
- Mutations in Ab gene diversity program
- UNG/MSH2 deficiencies block class switch (1)
- UNG/MSH2 deficiencies block class switch (2)
- AID deamination - conclusion
- Mistargeted gene rearrangements and cancer
- Generation of antibody diversity
- AID ancestors
- Other AID related proteins
- Comparing AID and dCMP DA
- APOBEC1 is involved in RNA editing
- APOBEC1 in apolipoprotein production
- APOBEC2 is as old as AID
- The evolution of AID and APOBEC proteins
- AID versus APOBEC3
- RIP - repeat-induced point mutation
- dC deamination and dC methylation
- 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:
Categories:
Therapeutic Areas:
Talk Citation
Neuberger, M. (2007, October 1). The generation of diversity in antibody genes [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 5, 2025, from https://doi.org/10.69645/BUDT3628.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Michael Neuberger has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.