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Immune system overview in 10 minutes The non-immunologist guide to the immune system Morten Nielsen Department of Systems Biology DTU. Vaccine development!.

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Immune system overview in 10 minutesThe non-immunologist guide to the immune systemMorten NielsenDepartment of Systems BiologyDTU

vaccine development
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).

vaccines have been made for 36 of 400 human pathogens
Vaccines have been made for 36 of >400 human pathogens

+HPV & Rotavirus

Immunological Bioinformatics, The MIT press.

immune system
Immune system
  • Innate – fast…
  • Addaptive – remembers…
    • Cellular
      • Cytotoxic T lymphocytes (CTL)
      • Helper T lymphocytes (HTL)
    • Humoral
      • B lymphocytes

Epitopes

Figure by Eric A.J. Reits

mhc class i pathway
MHC Class I pathway

Figure by Eric A.J. Reits

mhc i molecules present peptides on the surface of most cells
MHC-I molecules present peptides on the surface of most cells

Figure courtesy Mette Voldby Larsen

slide9

CTL response

Figure courtesy Mette Voldby Larsen

hla binding motif
HLA binding motif

SLLPAIVEL YLLPAIVHI TLWVDPYEV GLVPFLVSV KLLEPVLLL LLDVPTAAV LLDVPTAAV LLDVPTAAV

LLDVPTAAV VLFRGGPRG MVDGTLLLL YMNGTMSQV MLLSVPLLL SLLGLLVEV ALLPPINIL TLIKIQHTL

HLIDYLVTS ILAPPVVKL ALFPQLVIL GILGFVFTL STNRQSGRQ GLDVLTAKV RILGAVAKV QVCERIPTI

ILFGHENRV ILMEHIHKL ILDQKINEV SLAGGIIGV LLIENVASL FLLWATAEA SLPDFGISY KKREEAPSL

LERPGGNEI ALSNLEVKL ALNELLQHV DLERKVESL FLGENISNF ALSDHHIYL GLSEFTEYL STAPPAHGV

PLDGEYFTL GVLVGVALI RTLDKVLEV HLSTAFARV RLDSYVRSL YMNGTMSQV GILGFVFTL ILKEPVHGV

ILGFVFTLT LLFGYPVYV GLSPTVWLS WLSLLVPFV FLPSDFFPS CLGGLLTMV FIAGNSAYE KLGEFYNQM

KLVALGINA DLMGYIPLV RLVTLKDIV MLLAVLYCL AAGIGILTV YLEPGPVTA LLDGTATLR ITDQVPFSV

KTWGQYWQV TITDQVPFS AFHHVAREL YLNKIQNSL MMRKLAILS AIMDKNIIL IMDKNIILK SMVGNWAKV

SLLAPGAKQ KIFGSLAFL ELVSEFSRM KLTPLCVTL VLYRYGSFS YIGEVLVSV CINGVCWTV VMNILLQYV

ILTVILGVL KVLEYVIKV FLWGPRALV GLSRYVARL FLLTRILTI HLGNVKYLV GIAGGLALL GLQDCTMLV

TGAPVTYST VIYQYMDDL VLPDVFIRC VLPDVFIRC AVGIGIAVV LVVLGLLAV ALGLGLLPV GIGIGVLAA

GAGIGVAVL IAGIGILAI LIVIGILIL LAGIGLIAA VDGIGILTI GAGIGVLTA AAGIGIIQI QAGIGILLA

KARDPHSGH KACDPHSGH ACDPHSGHF SLYNTVATL RGPGRAFVT NLVPMVATV GLHCYEQLV PLKQHFQIV

AVFDRKSDA LLDFVRFMG VLVKSPNHV GLAPPQHLI LLGRNSFEV PLTFGWCYK VLEWRFDSR TLNAWVKVV

GLCTLVAML FIDSYICQV IISAVVGIL VMAGVGSPY LLWTLVVLL SVRDRLARL LLMDCSGSI CLTSTVQLV

VLHDDLLEA LMWITQCFL SLLMWITQC QLSLLMWIT LLGATCMFV RLTRFLSRV YMDGTMSQV FLTPKKLQC

ISNDVCAQV VKTDGNPPE SVYDFFVWL FLYGALLLA VLFSSDFRI LMWAKIGPV SLLLELEEV SLSRFSWGA

YTAFTIPSI RLMKQDFSV RLPRIFCSC FLWGPRAYA RLLQETELV SLFEGIDFY SLDQSVVEL RLNMFTPYI

NMFTPYIGV LMIIPLINV TLFIGSHVV SLVIVTTFV VLQWASLAV ILAKFLHWL STAPPHVNV LLLLTVLTV

VVLGVVFGI ILHNGAYSL MIMVKCWMI MLGTHTMEV MLGTHTMEV SLADTNSLA LLWAARPRL GVALQTMKQ

GLYDGMEHL KMVELVHFL YLQLVFGIE MLMAQEALA LMAQEALAF VYDGREHTV YLSGANLNL RMFPNAPYL

EAAGIGILT TLDSQVMSL STPPPGTRV KVAELVHFL IMIGVLVGV ALCRWGLLL LLFAGVQCQ VLLCESTAV

YLSTAFARV YLLEMLWRL SLDDYNHLV RTLDKVLEV GLPVEYLQV KLIANNTRV FIYAGSLSA KLVANNTRL

FLDEFMEGV ALQPGTALL VLDGLDVLL SLYSFPEPE ALYVDSLFF SLLQHLIGL ELTLGEFLK MINAYLDKL

AAGIGILTV FLPSDFFPS SVRDRLARL SLREWLLRI LLSAWILTA AAGIGILTV AVPDEIPPL FAYDGKDYI

AAGIGILTV FLPSDFFPS AAGIGILTV FLPSDFFPS AAGIGILTV FLWGPRALV ETVSEQSNV ITLWQRPLV

sequence logos
Sequence logos
  • Height of a column equal to I
  • Relative height of a letter is p
  • Highly useful tool to visualize sequence motifs

HLA-A0201

High information

positions

http://www.cbs.dtu.dk/biotools/Seq2Logo

hla specificity clustering
HLA specificity clustering

A0201

A0206

A0101

B0702

more mhc molecules more diversity in the presented peptides
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.
pathogen variability
Pathogen variability
  • Pathogen variability
    • Millions of viral particles within a given host
  • Pathogen diversity
    • Different viral subtypes circulating in different parts of the world
epitope identification
Epitope identification

56 (1.5%) 9mer are conserved

among all 15 Clade A gag

sequences

slide20

Viralescape/variation

The virus of today is different from the virus of tomorrow (Viral escape)

???

??

????

Figure courtesy Mette Voldby Larsen

vaccine design p olytope construction
Vaccine design. Polytope construction

Linker

NH2

M

COOH

Epitope

cleavage

C-terminal cleavage

New epitopes

Cleavage within epitopes