1. Immunogenetics Sadegh Babashah, PhD Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University

2. 2 History

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9. 9 123 Infection begins inflammatory response

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12. 12 Clonal selection hypothesis

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14. 14 Schematic representation of Ag receptors

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19. 19 Isolation of TCR molecule 1.Production of Mab against various T-cell clones 2.Screening these antibodies against different T-cell clones 3.Finding clone-specific Mab 4.Isolation of TCR by clone-specific Mab A. Monoclonal antibody (Mab)

20. 20 B. Cloning TCR genes 1.Isolation of mRNA from T-cell 2.Synthesis of cDNA 3.Hybridization of cDNA with B-cell mRNA for Isolation of T-cell specific cDNA by 4.Southern blotting with genomic DNA for finding rearranged cDNA 5.Rearranged cDNA is TCR gene Isolation of TCR molecule

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22. 22 Production of Lymphocyte Ag receptors (BCR, TCR)

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32. 32 Recombinase complex involved in V(D)J recombination: - Lymphocyte-specific recombinase (RAG-1 & RAG-2) - General enzymes (e.g. Ku heterodimer)

33. 33 The Non-homologous End-Joining repair Process (NHEJ)

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36. 36 T-cell receptor

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38. 38 α and β locuses in T-cell receptor gene TCRα: TCRβ:

39. 39 Rearrangement in T-cell receptor gene

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41. 41 تنوع ترکیبی + تنوع تلفیقی

42. 42 TCRα: TCRβ:

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44. TCRα: TCRβ: 44 TCRα (containing TCRδ): TCRγ: δ-chain locus ………..…..

45. 45 TCRα (containing TCRδ): δ-chain locus ………..…..

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50. 50 Pantameric IgM Dimeric IgA x 900’000

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59. 59 Thank you for listening, any comments?