immune system overview in 10 minutes the non-immunologist guide to the immune system morten nielsen...
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![Page 1: Immune system overview in 10 minutes The non-immunologist guide to the immune system Morten Nielsen Department of Systems Biology DTU](https://reader036.vdocuments.net/reader036/viewer/2022062307/551b07295503465e7d8b5adf/html5/thumbnails/1.jpg)
Immune system overview in 10 minutes
The non-immunologist guide to the immune system
Morten NielsenDepartment of Systems Biology
DTU
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Vaccine development!
The arm of Sarah Nelmes, a dairy maid, who had contracted cowpox. Jenner used material from her arm to vaccinate an eight year old boy, James Phipps. (1798).
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Vaccine review
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Vaccines can eradicate pathogens and save lives
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Vaccines have been made for 36 of >400 human pathogens
Immunological Bioinformatics, The MIT press.
+HPV & Rotavirus
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Immune system• Innate – fast…
• Addaptive – remembers…
• Cellular
• Cytotoxic T lymphocytes (CTL)
• Helper T lymphocytes (HTL)
• Humoral
• B lymphocytes
Figure by Eric A.J. Reits
Epitopes
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MHC Class I pathway
Figure by Eric A.J. Reits
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MHC-I molecules present peptides on the surface of most cells
Figure courtesy Mette Voldby Larsen
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CTL response
Figure courtesy Mette Voldby Larsen
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Encounter with death
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Figure by Anne Mølgaard
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HLA binding motif
SLLPAIVEL YLLPAIVHI TLWVDPYEV GLVPFLVSV KLLEPVLLL LLDVPTAAV LLDVPTAAV LLDVPTAAVLLDVPTAAV VLFRGGPRG MVDGTLLLL YMNGTMSQV MLLSVPLLL SLLGLLVEV ALLPPINIL TLIKIQHTLHLIDYLVTS ILAPPVVKL ALFPQLVIL GILGFVFTL STNRQSGRQ GLDVLTAKV RILGAVAKV QVCERIPTIILFGHENRV ILMEHIHKL ILDQKINEV SLAGGIIGV LLIENVASL FLLWATAEA SLPDFGISY KKREEAPSLLERPGGNEI ALSNLEVKL ALNELLQHV DLERKVESL FLGENISNF ALSDHHIYL GLSEFTEYL STAPPAHGVPLDGEYFTL GVLVGVALI RTLDKVLEV HLSTAFARV RLDSYVRSL YMNGTMSQV GILGFVFTL ILKEPVHGVILGFVFTLT LLFGYPVYV GLSPTVWLS WLSLLVPFV FLPSDFFPS CLGGLLTMV FIAGNSAYE KLGEFYNQMKLVALGINA DLMGYIPLV RLVTLKDIV MLLAVLYCL AAGIGILTV YLEPGPVTA LLDGTATLR ITDQVPFSVKTWGQYWQV TITDQVPFS AFHHVAREL YLNKIQNSL MMRKLAILS AIMDKNIIL IMDKNIILK SMVGNWAKVSLLAPGAKQ KIFGSLAFL ELVSEFSRM KLTPLCVTL VLYRYGSFS YIGEVLVSV CINGVCWTV VMNILLQYVILTVILGVL KVLEYVIKV FLWGPRALV GLSRYVARL FLLTRILTI HLGNVKYLV GIAGGLALL GLQDCTMLVTGAPVTYST VIYQYMDDL VLPDVFIRC VLPDVFIRC AVGIGIAVV LVVLGLLAV ALGLGLLPV GIGIGVLAAGAGIGVAVL IAGIGILAI LIVIGILIL LAGIGLIAA VDGIGILTI GAGIGVLTA AAGIGIIQI QAGIGILLAKARDPHSGH KACDPHSGH ACDPHSGHF SLYNTVATL RGPGRAFVT NLVPMVATV GLHCYEQLV PLKQHFQIVAVFDRKSDA LLDFVRFMG VLVKSPNHV GLAPPQHLI LLGRNSFEV PLTFGWCYK VLEWRFDSR TLNAWVKVVGLCTLVAML FIDSYICQV IISAVVGIL VMAGVGSPY LLWTLVVLL SVRDRLARL LLMDCSGSI CLTSTVQLVVLHDDLLEA LMWITQCFL SLLMWITQC QLSLLMWIT LLGATCMFV RLTRFLSRV YMDGTMSQV FLTPKKLQCISNDVCAQV VKTDGNPPE SVYDFFVWL FLYGALLLA VLFSSDFRI LMWAKIGPV SLLLELEEV SLSRFSWGAYTAFTIPSI RLMKQDFSV RLPRIFCSC FLWGPRAYA RLLQETELV SLFEGIDFY SLDQSVVEL RLNMFTPYINMFTPYIGV LMIIPLINV TLFIGSHVV SLVIVTTFV VLQWASLAV ILAKFLHWL STAPPHVNV LLLLTVLTVVVLGVVFGI ILHNGAYSL MIMVKCWMI MLGTHTMEV MLGTHTMEV SLADTNSLA LLWAARPRL GVALQTMKQGLYDGMEHL KMVELVHFL YLQLVFGIE MLMAQEALA LMAQEALAF VYDGREHTV YLSGANLNL RMFPNAPYLEAAGIGILT TLDSQVMSL STPPPGTRV KVAELVHFL IMIGVLVGV ALCRWGLLL LLFAGVQCQ VLLCESTAVYLSTAFARV YLLEMLWRL SLDDYNHLV RTLDKVLEV GLPVEYLQV KLIANNTRV FIYAGSLSA KLVANNTRLFLDEFMEGV ALQPGTALL VLDGLDVLL SLYSFPEPE ALYVDSLFF SLLQHLIGL ELTLGEFLK MINAYLDKLAAGIGILTV FLPSDFFPS SVRDRLARL SLREWLLRI LLSAWILTA AAGIGILTV AVPDEIPPL FAYDGKDYIAAGIGILTV FLPSDFFPS AAGIGILTV FLPSDFFPS AAGIGILTV FLWGPRALV ETVSEQSNV ITLWQRPLV
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Sequence logos
•Height of a column equal to I•Relative height of a letter is p•Highly useful tool to visualize sequence motifs High information
positions
HLA-A0201
http://www.cbs.dtu.dk/biotools/Seq2Logo
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HLA polymorphism
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HLA specificity clustering
A0201
A0101
A0206
B0702
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More MHC molecules: more diversity in the presented peptides
• 1% probability that MHC molecule presents a peptide• Different hosts sample different peptides from same pathogen.
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Pathogen variability
• Pathogen variability– Millions of viral particles within a given
host
• Pathogen diversity– Different viral subtypes circulating in
different parts of the world
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HIV subtypes (Gag protein)
C
B
AE
A
D
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Epitope identification
56 (1.5%) 9mer are conserved among all 15 Clade A gag
sequences
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Viral escape/variation
Figure courtesy Mette Voldby Larsen
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The virus of today is different from the virus of tomorrow (Viral escape)
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Vaccine design. Polytope construction
NH2 COOH
Epitope
Linker
M
C-terminal cleavage
Cleavage within epitopes
New epitopescleavage
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DNA vaccine