Lymphocyte lineages The lymphocyte surface without the an7gen receptor

Transcription

1 2 Lymphocyte lineages The lymphocyte surface without the an7gen receptor

2 INNATE, adapta6on during evolu6on ADAPTIVE, adapta6on during one s life Liver Epithelia Macrophages Granulocytes Acute phase Pentraxins Intracellular systems RIG1, PKR, NLR, TRIM Phagocytosis Scav R. Mannose R. Lec6n R. (LRR) TLR/(IgSF) IL1R TIR Effectors: AMP, Cytokines, PDC Type I IFN NK C Lymphocytes Co receptors Co s6mulators Fc receptors ITIM Cytokines Chemokines Lymphoid organs RAG T- B IgSF AID APC Thymus, BM, Random rep.select. MHC pres. Clonal selec6on Effectors:Abs, CTLs,T- help specificity,memory regula6on Affinity matura6on A constella6on: many modules not necessarily linked to one another A system: Centered on lymphocytes locked in a coevolu6onary unit Immunity in man

3 (Drawn from the content of the next 4 slides)

4 h?p://seer.cancer.gov/tools/heme/webinars/03_lineages1.pdf Hematopoie7c cell lineages

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6 Nat Rev Immunol Feb;13(2): doi: /nri3349. Epub 2013 Jan 7.

7 h?p://what- when- how.com/acp- medicine/organs- and- cells- of- the- immune- system- part- 1/ Lineages of cells of the immune system and of blood cells all begin with the stem cell. Stem cells that differen6ate to generate B cells reside in the bone marrow, and those that produce T cells migrate from the bone marrow to the thymus. T cell matura6on involves the progressive expression of selected cell surface markers and the ac6va6on of various genes, including α β γ, and δ genes that code for the chains that make up the ap and y8 T cell receptors (TCRs). Posi6ve and nega6ve selec6on of T cells occurs at the so- called double- posi6ve (CD4+,CD8+) stage. Natural killer cells develop both in the bone marrow and in the thymus.

8 anus DEUTEROSTOME mouth PROTOSTOME GNATHOSTOMES AGNATHANS Petromyzon CEPHALOCHORDATES Branchiostoma UROCHORDATES Ciona HEMICHORDATES ECHINODERMS Strongylocentrotus PLATHYHELMINTHS ANNELIDS MOLLUSKS Biomphalaria NEMERTEANS SIPUNCULIDS VERTEBRATES INVERTEBRATES NEMATODES ARTHROPODS Anopheles Drosophila Penaeus CNIDARIA Protozoa PORIFERA PLACOZOA

9 In red: Mesoderm deriva7ves Hartenstein V. Annu. Rev. Cell Dev.Biol : Hematopoiesis across metazoan phyla

10 Transcrip7on factors A transcrip7on factor (some7mes called a sequence- specific DNA- binding factor) is a protein that binds to specific DNA sequences adjacent to the genes that they regulate via one or more DNA- binding domains (DBDs), thereby controlling the rate of transcrip7on of gene7c informa7on from DNA to messenger RNA. Transcrip7on factors perform this func7on alone or with other proteins in a complex, by promo7ng (as an ac7vator), or blocking (as a repressor) the recruitment of RNA polymerase (the enzyme that performs the transcrip7on of gene7c informa7on from DNA to RNA) to specific genes.

11 Cnidaria (Hydra) All major signalling pathways, that are known in bilaterian to play a role in stem cell differen7a7on, have been found in cnidarians. In red: Hematopoie7c 7ssues, mesoderm deriva7ves

12 In red: Hematopoie7c 7ssues

13 Annu. Rev. Cell Dev.Biol : Mammalian lymphocyte Insect hemocytes Division of the work hematopoei7c lineages, of mesodermic origin

14 Solek C and JP Rast

15 anus DEUTEROSTOME mouth PROTOSTOME GNATHOSTOMES AGNATHANS Petromyzon CEPHALOCHORDATES Branchiostoma UROCHORDATES Ciona HEMICHORDATES ECHINODERMS Strongylocentrotus PLATHYHELMINTHS ANNELIDS MOLLUSKS Biomphalaria NEMERTEANS SIPUNCULIDS VERTEBRATES INVERTEBRATES NEMATODES ARTHROPODS Anopheles Drosophila Penaeus CNIDARIA Protozoa PORIFERA PLACOZOA

16 Heterodontus Petromyzon Ciona Branchiostoma In red: Hematopoie7c 7ssues

17 Lymphocyte lineages in jawless and jawed vertebrates M.Flajnik, Current Biology 24, R1060 R1065, November 3, 2014

18 The leukocyte surface First Many molecules defining a context of interac7ons.(igsf) One example: an7gen presen7ng cells and T lymphocytes. Then An7gen specific receptors of lymphocytes

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20 The lymphocyte an APC surfaces An7gen Presen7ng Cell CD200R CD80/86 CD58 CD48 SLAM6 SLAM7 SLAM CD84 CD40 CD166 CD47 MHC ClassII TIM4 ICAM CD22 CD200 CD28 CTLA4 BTLA CD2 CD244 SLAM6 SLAM7 SLAM CD84 CD40L SIRPγ CD4 TCR CD3γδε LFA1 CD45 CD52 T Cell CD6, 5 TIM1 Homologies between invertebrates IgSF members and Vertebrates IgSF coreceptors

21 Position on human chromosomes of homologs of Invertebrates and Agnathan IgSF members (see next slide) distributed on 4 paralogues * involved in the T/APC interactions of the previous slide" Chr 1p13/q22 Chr3q p12/q13 Chr11q23-25 CH21q21-22 CD52 LRIg1 LRIg2 Roundabout-like2 CD58 Robo1 CD2 * Igsf4 nectin FPRP CD101 B7H4 B7x centromere centromere centromere centromere Igsf4b nectin CD166 CD6 CXADR CTX JAM SLAMf9 * CD47CTX JAM * CD5 * NCAM2 Igsf4B Nectin 3 PVRL3 JAM2 JAM CTX PGRL CD96 Amalgam * NCAM1 CD56 Igsf5 VSIg8 CTX JAM CD200 Necl-2 nectin DSCAM SLAMf7 BTLA CD272 * DSCAML1 ICOS L CD48 CD200R1 AMICA CTXJAM CD18 Ly-9 LSAMP Amalgam EVA1 CD244 Igsf11 CTX JAM CD3E PVLR4 nectin Uroplakin 1b CD3D JAM1 JAM CTX CD80 * CD3G A33 CTX JAM CD86 UPK2 * CD3Z MCAM CD45 * CD90 PVRL1 nectin CRTAM nectin * ASAM CTX JAM (ChrXq22) CTH CTX JAM (Chr19 q13) Z39Ig JAM CTX ESAM CTX JAM CD22 CTXHumX CTX JAM ROBO3 UPK1A ROBO4 Igsf4c nectin Neurotrimin PVR CD155 nectin OBCAM Amalgam CD112 nectin JAM3 JAM CTX LRC Du Pasquier L.et al (2004) Imm. Rev.198: Du Pasquier L. (2005) Science 309: unpublished" * * * *

22 (Du Pasquier L CTMI (2000) 248: " Du Pasquier L.et al (2004) Imm. Rev.198: ) " C.i CTX/JAM-L" V C2! TM" Cyto C.i Nectin-L V C1-l! C2! TM" Cyto C.i CD 166-L! (CD6 ligand)" V S-S C2! C2! C2! S-S C2! TM" Cyto B.l. VCnp. (CTX/JAM-L)! (Yu et al 2005 JI 174: )" V C2! TM" Cyto ITIM B.l VCTX-L! CD 47-L (SIRP ligand)! (Sato A et al 2003 Immunogenetics 55:423-7)" V TCR and BCR basic units V C1-l! TM" Cyto

23 IgSF lymphocyte receptors in Cyclostomes and cephalochordates (Pancer et al PNAS , Suzuki et al DCI 28: , Yu et al J.I.174: , Cannon et al, Img 56: Sato et al, Img 55: 423-7) Lamprey TCR Protoype (CTX type) " V C2! TM" Cyto ITIM Nectin V C1-l! C2! TM" V-Pre B (P0, V CTX ) V! Hagfish CTX type " V C2! TM" Cyto ITIM (CTX/CD33 type) NICIR V C2! TM" Cyto ITAM APAR A" " " APAR B V! V! TM R" TM" Cyto Cyto ITIM

24 1R 2R Generation of paralogs" Ohno s hypothesis 1970

25 Evolu7on of Chordates

26 Evolu7on of Vertebrates

27 Lymphocyte - like cells of Ciona express (in situ hybridiza7on) IgSF members (CTX or nec7ns) related to some leukocyte receptors of Vertebrates