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MHC sequencing project

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Presentation on theme: "MHC sequencing project"— Presentation transcript:

1 MHC sequencing project
GenBank submission A. 800 CDS accessions for alleles of non-IPD curated genes (GenBank) B. 190 gene sequence alleles of IPD non-classical genes (GenBank) Update to (A) to full gene sequences (GenBank) and alignments (GitHub)

2 MHC sequencing project

3 MHC sequencing project

4

5 MHC sequencing project
330 visits; referring sites

6 KIR Polymorphism Workshop

7 Dynamic interactions of KIR and HLA class I underlie significant pressure to evolve
Paul J. Norman Parham Lab Stanford

8 KIR and HLA have co-evolved to diversify their interaction
Computer modeling Phylogenetics Cross-species comparison Population Genetics HLA KIR Binding site Norman et al PloS Genetics

9 Multiple binders/functions of HLA
KIR LILR TCR + peptide (HLA-E) Computer modeling Phylogenetics Cross-species comparison Population Genetics HLA-C

10 But KIR only have one job..
(e.g.) 2DL1*022 evolved in response to high C2 frequency Hilton et al. 2015 PLoS Genetics; 11:

11 High-resolution KIR and HLA class I Genotypes
KIR Polymorphism Workshop High-resolution KIR and HLA class I Genotypes

12 KIR Polymorphism Workshop
KhoeSan Pygmy Hadza West African Africa Modern humans Out of Africa

13 KIR Polymorphism Workshop
Bari et al. 2009 Blood Hilton et al J. Immunol

14 KIR Polymorphism Workshop

15 KIR Polymorphism Workshop

16 KIR Polymorphism Workshop

17 Han HLA Class I haplotypes
All of top 10 encode at least 2 KIR ligands

18 Except East Asian and South American

19 (has novel amino acids at two positively-selected residues)
An unusual KIR allele shared by Māori, Papua New Guineans and Indigenous Australians (has novel amino acids at two positively-selected residues) Residue 166 Residue 20 2DL4 3DL1 2DS4 3DL2 *028 *086 *001 *002 Maori/PPNG Haplotype *001loh *002loh *00104 *00501 Australian Haplotypes Nemat-Gorgani et al Immunogenetics Loh et al. in prep

20 KIR3DL1; F166 and Q20 enhance recognition of target HLA
3DL1 _L166 3DL1_F166 3DL1_F166_Q20 (*086) Relative activity Effector: Jurkat cells with KIR3DL1+CD3ζ Target: HLA transfected [Philippa Saunders]

21 KIR Polymorphism Workshop


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