The evolution of the
This presentation is the property of its rightful owner.
Sponsored Links
1 / 18

Lucas Kemper 17.01.2011 PowerPoint PPT Presentation


  • 68 Views
  • Uploaded on
  • Presentation posted in: General

The evolution of the adaptive immune system. Lucas Kemper 17.01.2011. Introduction. Lamprey. Shark. big bang theory. conventional adaptive immunity. Jawless vertebrate. Jawed vertebrate. Introduction. Lamprey. Shark. I have:. What does he has that I don’t have?.

Download Presentation

Lucas Kemper 17.01.2011

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Lucas kemper 17 01 2011

The evolution of the

adaptive immune system

Lucas Kemper

17.01.2011


Lucas kemper 17 01 2011

Introduction

Lamprey

Shark

big bang

theory

conventional

adaptive

immunity

Jawless vertebrate

Jawed vertebrate


Lucas kemper 17 01 2011

Introduction

Lamprey

Shark

I have:

What does he has

that I don’t have?

RAG mediated rearranging

of antigen receptors

(for my B and T cells)

further mechanisms for

receptor diversification

MHC molecules

(and much more)


Lucas kemper 17 01 2011

Introduction

jawless

vertebrates

Conventional adaptive

immunity

jawed vertebrates

invertebrates

RAG mediated rearranging

of antigen receptors

further mechanisms for

receptor diversification

MHC molecules


Lucas kemper 17 01 2011

RAG mediated rearranging of antigen receptors

V(D)J recombination – state of the art

locus of

TCR α-chain

in germline-DNA

randomly recombined DNA

αβ T cell receptor

randomly recombined DNA

locus of

TCR β-chain

in germline-DNA


Lucas kemper 17 01 2011

RAG mediated rearranging of antigen receptors

V(D)J recombination – state of the art

germline configuration

terminal deoxynucleotidyl

transferase (TdT)

RAG complex binds recombination signal sequence

RAG complexes arrange next to each other

RAG complex cleaves DNA and hairpins are formed

Endonucleases open the hairpin randomly

Random nucleotides are added by TdT and/or deleted by endonucleases

Ligation of DNA


Lucas kemper 17 01 2011

RAG mediated rearranging of antigen receptors

V(D)J recombination – the origin of this mechanism

first mechanism

leading to variable immune receptors

RAG-like transposon

  • excision of transposon

Common ancestor

of all jawed vertebrates

  • imprecise sealing

  • of the gap

 clonaly diverse specifities

Integration in ancestral immunoglobulin gene locus*

*nature unclear

*maybe innate immune receptor


Lucas kemper 17 01 2011

RAG mediated rearranging of antigen receptors

V(D)J recombination – the origin of this mechanism

first mechanism

leading to variable immune receptors

RAG-like transposon

Common ancestor

of all jawed vertebrates

Recombination and

gene duplication

Integration in ancestral immunoglobulin gene locus*

RAG location outside

of Ig and TCR loci

RSS elements

remained in

Ig and TCR loci

Gene segments in

Ig and TCR loci

locus duplication

tandem duplication

differentiation


Lucas kemper 17 01 2011

Further mechanisms for receptor diversification

jawed vertebrates have many

novel mechanisms and molecules

that are involved in adaptive immunity

compared with jawless fish

Lamprey

Shark

Jawless vertebrate

Jawed vertebrate

Expansion of the potential of V D J recombination


Lucas kemper 17 01 2011

Further mechanisms for receptor diversification

germline configuration

terminal deoxynucleotidyl

transferase (TdT)

terminal deoxynucleotidyl transferase (TdT)

lymphocyte-specific template-independent DNA polymerase

introduces untemplated nucleotides at the junctions of V, D and J segments

thereby TdT increases diversity

not found in jaweless vertebrates or below


Lucas kemper 17 01 2011

MHC molecules

MHC molecules present antigen to αβTCR on T cells

What was first?

hen

or

egg

rearranging αβTCR

or

antigen processing and

presentation by MHC


Lucas kemper 17 01 2011

MHC molecules

MHC molecules present antigen to αβTCR on T cells

What was first?

αβTCR and MHC appeared at the same time in evolution

no αβTCR and MHC outside of jawed vertebrates

therefore it is difficult to answer what was first

rearranging αβTCR

or

antigen processing and

presentation by MHC

Igs and BCR arose

before TCR and MHC

explenatation for the development

of an TCR-MHC system

  • maybe derived from phagocytosis

  • and lysosomal processing

  • using VDJ recombination to

  • recognize intracellular antigens


Lucas kemper 17 01 2011

End of the story?

Lamprey

Shark

Lamprey

But I am not helpless!

Ha, I am so cool!

I can also mount an

adaptive immune response

in the absence of

BCR, TCR and MHC


Lucas kemper 17 01 2011

A convergent adaptive IS of jawless vertebrates

Jawless vertebrates

Jawed vertebrates

Shark

Lamprey


Lucas kemper 17 01 2011

A convergent adaptive IS of jawless vertebrates

main features of the convergent

adaptive immune system

Jawless vertebrates

germline VLR lacks LRR modules

generation of diversity by rearranging

LRR modules into the VLR gene

RAG-independent process

a single VLR gene can have combinatorial diversity comparable to that of Igs

Two VLR genes known

(membrane-bound and secreted)

two populations of lymphoid cells that seem to be

functionally similar to the T and B cells

variable lymphocyte receptor = VLR

leucin rich repeats = LRR


Lucas kemper 17 01 2011

Conclusions

jawless and jawed fish both have an AIS based on different gene families

BCR–TCR–MHC‑based system

is more complex

RAG transposon had major role in the emergence of the jawed vertebrate AIS

jawless

vertebrates

invertebrates

jawed vertebrates

What about the big bang theory?

Still holds true for conventional

adaptive immunity

(BCR, TCR, MHC)

but

“could be more a set of observations made from a limited phylogenetic sampling and mechanistic focus than a true representation of rapid evolution”


Lucas kemper 17 01 2011

Conclusions

jawless and jawed fish both have an AIS based on different gene families

BCR–TCR–MHC‑based system

is more complex

RAG transposon had major role in the emergence of the jawed vertebrate AIS

jawless

vertebrates

invertebrates

jawed vertebrates

What about the evolutionary

pressures for adaptive immunity?

large predatory jawed vertebrates

have usualy few offsprings

adaptive immune system for

higher surival rate of offsprings?


Lucas kemper 17 01 2011

Thank you


  • Login