1、The Diversity of Immunoglobulin,Yan Wang,Supervisor: Andrew Collins Cosupervisor: William Sewell,Immunoglobulin,Structures Heavy chain and light chain(and ) Constant region Class: IgA, IgD, IgE, IgG and IgM Variable region Antigen binding site,Generation of diversities,AID,N-Regions,Part 1,Immunoglo

2、bulin germline gene repertoire study,IGHV gene repertoire,Highly polymorphic 226 reported genes and allelic variants 104 was reported in error 12 putative new polymorphisms, 3 have been sequenced Conclusion: The existing IGHV gene repertoire is full of incorrectly reported sequences.,IGKV gene reper

3、toire analysis,Compilation of Database 1863 rearranged IGKV sequences from the EMBL 66 germline genes from the IMGT Alignments using Smith-Waterman algorithm. Unreported IGKV alleles IGKV alleles with low number of unmutated sequences were collected Multiple alignment Shared mismatches Sequencing fr

4、om genomic DNA,Junction analysis of IGK genes,435 low mutation sequences (3 IGKV mutations) were realigned to determine IGKJ genes using V-QUEST VJ gene useage N-Region,Results,5 reported genes may be the result of sequencing errors IGKV1D-13*01 and IGKV1-37*01 may be functional in some individuals

5、Unreported polymorphisms: IGKV1-16*02 and IGKV2-30*02. The existing IGKV repertoire is relatively complete and accurate,Conclusions,Not only is there little diversity in the germline genes of the kappa locus, but little junctional diversity is generated during the process of gene rearrangement. The

6、immunoglobulin gene repertoire can therefore be characterised as having extraordinary diversity in the heavy chain, and limited diversity in the light chain.,Part 2,Sequencing immunoglobulin genes from allergic and parasitised individuals,IgE and Allergy,Natural function of IgE Parasite infections I

7、gE and Allergic disease Antigen selection in IgE The relationship between IgE and IgG4,Understanding IgE mutations in PNG,PNG IgE vs PNG IgG Other Factors Exposure to pathogens Age,Two Questions,Is there a higher level of mutation in antibodies of PNG villagers, compared to Australia urban individuals? Are higher numbers of mutations seen in older individuals?,Acknowledgements,Andrew Collins William Sewell Katherine Jackson