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T CELL-MEDIATED CYTOTOXICITY POSTER REFERENCES, DECEMBER 2004

Immunological Synapse Illustration

  • Iwashima, M. et al. (1994) Science 263:1136. Lck activity leads to ZAP-70 recruitment.
  • Jacobelli, J. et al. (2004) Curr. Opin. Immunol. 16:345. Recent review describing immune synapse-associated molecular interactions.
  • Kuhn, J.R. & M. Poenie (2002) Immunity 16:111. Polarization of the MTOC and microtubules and localization of synapse-associated adhesion molecules.
  • O’Keefe, J.P. et al. (2004) Proc. Natl. Acad. Sci. USA 101:9351. PKC q and ZAP-70 accumulate at the CTL immune synapse.
  • Stinchcombe, J.C. et al. (2001) Immunity 15:751. Evidence for the presence of secretory and signaling domains surrounded by adhesion molecules at the CTL synapse.
  • van Oers, N.S. et al. (1996) J. Exp. Med. 183:1053. CD3 ITAM is Phosphorylated by Lck.

Cytolytic Granule Contents Illustration

Granzyme A

  • Beresford, P.J. et al. (1999) Immunity 10:585. Granzyme A elicits Caspase-independent nuclear condensation, membrane blebbing, and DNA nicks.
  • Fan, Z. et al. (2003) Nat. Immunol 4:145. APE of the SET complex is a Granzyme A substrate.
  • Fan, Z. et al. (2002) Mol. Cell. Biol. 22:2810. HMG2 of the SET complex is a Granzyme A substrate.
  • Fan, Z. et al. (2003) Cell 112:659. SET is a Granzyme A substrate that releases NM23-H1 to cause DNA nicks when cleaved. The SET complex translocates from ER to nucleus.
  • Lieberman, J. & Z. Fan. (2003) Curr. Opin. Immunol. 15:553. Recent review highlighting molecular interactions and mechanisms underlying Granzyme A-mediated apoptosis.
  • Zhang, D. et al. (2001) J. Biol. Chem. 276:3683. Histones are Granzyme A substrates.
  • Zhang, D. et al. (2001) Proc. Natl. Acad. Sci. USA 98:5746. Lamins A-C are Granzyme A substrates.

Granzyme B

  • Andrade, F. et al. (2001) Immunity 14:751. Viral protein L4-100kDa inhibits Granzyme B activity.
  • Cartier, A. et al. (2003) Cell Death Differ. 10:1320. HSV protein US3 inhibits Granzyme B activity.
  • Goping, I.S. et al. (2003) Immunity 18:355. SMAC/Diablo released from the mitochondria in response to Granzyme B.
  • Han, J. et al. (2004) J. Biol. Chem. 279:22020. Granzyme B and/or Caspase-3 cleavage of Mcl-1 releases pro-apoptotic BIM and mitochondrial Cytochrome c.
  • Heibein, J.A. et al. (2000) J. Exp. Med. 192:1391. Granzyme B cleaves BID, recruiting Bax to the mitochondria.
  • Heibein, J.A. et al. (1999) J. Immunol. 163:4683. Granzyme B elicits Perforin-dependent Cytochrome c release and δ?m.
  • Medema, J.P. et al. (1997) Eur. J. Immunol. 27:3492. Procaspase-8 is a Granzyme B substrate.
  • Metkar, S.S. et al. (2003) J. Cell Biol. 160:875. Procaspase-3 is a substrate of Granzyme B.
  • Quan, L.T. et al. (1995) J. Biol. Chem. 270:10377. Viral protein CrmA inhibits Granzyme B.
  • Sutton, V.R. et al. (2003) Immunity 18:319. SMAC/Diablo and HtrA2/OMI are released from the mitochondria in response to Granzyme B.
  • Sharif-Askari, E. et al. (2001) EMBO J. 20:3101. ICAD is a Granzyme B substrate.
  • Thomas, D.A. et al. (2000) Immunity 12:621. ICAD is a Granzyme B substrate.
  • Zhang, D. et al. (2001) Proc. Natl. Acad. Sci. USA 98:5746. Lamin B is a Granzyme B substrate.

Perforin

  • Browne, K.A. et al. (1999) Mol. Cell. Biol. 19:8604. Endosmolytic agents mimic Perforin’s role in mediating Granzyme entry into the cytosol.
  • Catalfamo M. & P.A. Henkart (2003) Curr. Opin. Immunol. 15:522. Review highlighting the role of Perforin in granule-mediated cytotoxicity.
  • Froelich, C.J. et al. (1996) J. Biol. Chem. 271:29073. Endosmolytic agents mimic Perforin’s role in mediating Granzyme B mediated apoptosis.
  • Topham D.J. et al. (1997) J. Immunol. 159:5197. CTLs use Fas and/or Perforin-dependent mechanisms in defense of influenza virus.
  • Young, J.D. et al. (1986) Cell 44:849. Perforin forms Ca 2+-dependent pores in lipid membranes.

Cytolytic Granule Contents Table

Granzymes

  • Garcia-Sanz, J.A. et al. (1988) J. Immunol. 64:129. Granzyme C in the cytolytic granule.
  • Hameed, A. et al. (1988) J. Immunol. 141:3142. Granzymes K (Granzyme 3) in the cytolytic granule.
  • Jenne, D. et al. (1989) J. Immunol. 140:318. Granzymes C in the cytolytic granule.
  • Jenne, D. et al. (1989) Biochemistry 28:7953. Granzymes G in the cytolytic granule.
  • Jenne, D. et al. (1988) Proc. Natl. Acad. Sci. USA 85:4814. Granzymes D, E, and F in the cytolytic granule.
  • Krahenbuhl, O. et al. (1988) J. Immunol. 141:3471. Granzymes A and B in the cytolytic granule.
  • Masson, D. et al. (1986) FEBS Lett. 208:84. Granzyme A in the cytolytic granule.
  • Peters, P.J. et al. (1991) J. Exp. Med. 173:1099. Granzymes B, D, E, F in the cytolytic granule.
  • Sayers, T.J. et al. (2001) J. Immunol. 166:765. Granzyme M in the cytolytic granule.
  • Sedelies, K.A. et al. (2004) J. Biol. Chem. 279:26581. Granzyme H in the cytolytic granule.

Perforin

  • Catalfamo M. & P.A. Henkart (2003) Curr. Opin. Immunol. 15:522. Recent review highlighting the role of Perforin in granule-mediated cytotoxicity.
  • Young, J.D. et al. (1986) J. Exp. Med. 164:144. Perforin purified from granules forms pores in vitro.

Calreticulin

  • Fraser, S.A. et al. (2000) J. Immunol. 164:4150. Perforin lytic activity is controlled by Calreticulin.
  • Andrin, C. et al. (1998) Biochemistry 37:10386. Calreticulin targeted to the granule.

Cathepsin B

  • Balaji, K.N. et al. (2002) J. Exp. Med. 196:493. Surface Cathepsin B protects effector cell after degranulation.

Cathepsin C

  • Pham, C.T.N. & Ley, T.J. (1999) Proc. Natl. Acad. Sci. USA 96:8627. Cathepsin C is required for Granzyme B processing and activation.

Granulysin

  • Pena, S.V. et al. (1997) J. Immunol. 158:2680. Granulysin localized to the granule.
  • Stenger, S. et al. (1998) Science 282:121. Granulysin-mediated killing of intracellular pathogens.
  • Kaspar, A.A. et al. (2001) J. Immunol. 167:350. Granulysin-mediated Cytochrome c release and apoptosis.

H+ ATPase

  • Kataoka, T. et al. (1994) J. Immunol. 153:3938. Acidification by H+ ATPase is critical for a normal functioning cytolytic granule.

Fas Ligand

  • Bossi, G. & G.M. Griffiths (1999) Nat. Med. 5:90. Degranulation and cell surface expression of Fas Ligand.
  • Kojima, Y. et al. (2002) Biochem. Biophys. Res. Commun. 296:328. Fas Ligand in the granule contributes to cell-mediated cytotoxicity.

Chemokines

  • Iijima, W. et al. (2003) Am. J. Pathol. 163:261. RANTES/CCL5 and IP-10/CXCL10 in the granule.
  • Wagner, L. et al. (1998) Nature 391:908 MIP -1 a /CCL3 and RANTES/CCL5 in the granule.

Serglycin

  • Galvin, J.P. et al. (1999) J. Immunol. 162:5345. Properties of Granzyme B/Serglycin complexes.
  • Metkar, S.S. et al. (2002) Immunity 16:417. Granzyme B exists in complex with Serglycin.

Bcl-2 Family Illustration

  • Desagher, S. et al. (1999) J. Cell Biol. 144:891. BID induces Bax-mediated release of mitochondrial Cytochrome c. Inhibited by Bcl-2 and Bcl-xL.
  • Finnegan, N.M. et al. (2001) Br. J. Cancer 85:115. Bcl-2/BAK interaction suppresses BAK-driven apoptosis.
  • Johnson B.W. et al. (2000) J. Biol. Chem. 275:31546. Bcl-xL inhibits death receptor-induced Cytochrome c release.
  • Puthalakath, H. et al. (1999) Mol. Cell 3:287 BIM is sequestered in the dynein/microtubule complex and released by apoptotic stimuli.
  • Terradillos, O. et al. (2002) FEBS Lett. 522:29. BIM inhibits Bcl-2 and Bcl-x L.
  • Wei, M.C. et al. (2000) Genes Dev. 14:2060. Fas ligation cleaves BID allowing tBID-mediated BAK-dependent Cytochrome c release.
  • Wei, M.C. et al. (2000) Science. 292:727. Bax and BAK homo-oligomerization is downstream of tBID and mediates Cytochrome c release.
  • Wolter, K.G. et al. (1997) J. Cell Biol. 139:1281. Bax moves from the cytosol to the OMM during apoptosis.
  • Yang, J. et al. (1997) Science 275:1129. Bcl-2 inhibits mitochondrial Cytochrome c release.

Bcl-2 Family Table

  • Borner, C. (2003) Mol. Immunol. 39:615. Review addressing Bcl-2 family structures, molecular interactions, and roles in apoptosis.
  • Festjens, N. et al. (2004) Acta Haematol. 111:7. Review addressing Bcl-2 family structures, molecular interactions, and roles in apoptosis.
  • Kataoka, T. et al. (2001) J. Biol. Chem. 276:19548. Identification, structure, and activity of Bcl-rambo.
  • Schmitt, E. et al. (2004) Oncogene 23:3915. Identification, structure, and activity of Bcl-x ES.

IAP Family & Inhibitors Illustration/Table

IAP General

  • Nachmias, B. et. al. (2004) Semin. Cancer Biol. 14:231. General IAP family review highlighting protein structures and molecular interactions.

Apollon/Bruce

  • Bartke, T. et al. (2004) Mol. Cell 14:801. Bruce inhibits Caspase-3 activity.
  • Hao, Y. et al. (2004) Nat. Cell Biol. 6:849. Apollon ubiquitinates Caspase-9 and SMAC.

cIAP-1 and cIAP2

  • Deveraux, Q.L. et al. (1998) EMBO J. 17:2215. cIAP-1, cIAP-2, and XIAP inhibit Caspase-3 and Caspase-9.
  • Herrera, B. et al. (2002) FEBS Lett. 520:93. cIAP-2 is a Caspase substrate during apoptosis.
  • Huang, H. -k. et al. (2000) J. Biol. Chem. 275:26661. cIAP-2 Promotes ubiquitination of Caspase-3 and Caspase-7.
  • Roy, N. et al. (1997) EMBO J. 16:6914. cIAP-1 and cIAP-2 Inhibit Caspases-3 and -7.

Livin

  • Kasof, G.M. & B.C. Gomes (2001) J. Biol. Chem. 276:3238. Livin binds Caspase-3 and Caspase-7, and inhibits Caspase-9 activity in vitro.

ILP-2

  • Richter, B.W. et al. (2001) Mol. Cell. Biol. 21:4292. Demonstrate specificity of ILP-2 for Caspase-9.

NAIP

  • Davoodi, J. et al. (2004) J. Biol. Chem. 279:40622. NAIP requires ATP to bind Caspase-9.
  • Maier, J.K.X. et al. (2002) J. Neurosci. 22:2035. NAIP binds Caspase-3 and Caspase-7.

SMAC/Diablo & HtrA2/Omi

  • Du, C. et al. (2000) Cell 102:33. Identification of SMAC as an IAP inhibitor.
  • Goping, I.S. et al. (2003) Immunity 18:355. SMAC/Diablo released from the mitochondria in response to Granzyme B.
  • Hegde, R. et al. (2002) J. Biol. Chem. 277:432. HtrA2/OMI suppresses IAP activity.
  • Song, Z. et al. (2003) J. Biol. Chem. 278:23130 Survivin-interaction with Smac/Diablo is important for Survivin inhibition of apoptosis.
  • Verhagen, A.M. et al. (2000) Cell 102:43. Identification of Diablo as an IAP inhibitor.
  • Verhagen, A.M. et al. (2002) J. Biol. Chem. 277:445. HtrA2/OMI suppresses IAP activity.

Survivin

  • Giodini, A. et al. (2002) Cancer Res. 62:2462. Survivin regulates microtubule stability.
  • O’Connor, D.D. et al. (2000) Proc. Natl. Acad. Sci. USA 97:13103. Survivin in complex with Caspase-9.
  • Tamm, I. et al. (1998) Cancer Res. 58:5315. Survivin binds Caspase-3 and Caspase-7 and inhibits Caspase activity.
  • Song, Z. et al. (2003) J. Biol. Chem. 278:23130. Survivin-interaction with SMAC/Diablo is important for apoptosis inhibition.

XIAP

  • Datta, R. et al. (2000) J. Biol. Chem. 275:31733. XIAP inhibits Caspase-3 and Caspase-9.
  • Deveraux, Q.L. et al. (1998) EMBO J. 17:2215. cIAP-1, cIAP-2, and XIAP inhibit Caspase-3 and Caspase-9.
  • Deveraux, Q.L. et al. (1999) EMBO J. 18:5242. XIAP BIR domains exhibit specificity for inhibition of Caspases-3, -7, and -9.
  • Johnson, D.E. et al. (2000) Cancer Res. 60:1818. XIAP is a substrate for Caspase-3 and Caspase-7.
  • Srinivasa, M. et al. (2003) J. Biol. Chem. 278:31469. XIAP is a substrate for HtrA2/OMI.
  • Suzuki, Y. et al. (2001) Proc. Natl. Acad. Sci. USA 98:8662. XIAP promotes Caspase-3 ubiquitination.

Caspases & Apoptosome Illustration

  • Acehan, D. et al. (2002) Mol. Cell 9:423. Three-dimensional structure of the apoptosome.
  • Boldin, M.P. et al. (1996) Cell 85:803. FADD as an adaptor involved in Caspase-8 recruitment to the TNF- a R1 receptor/Fas DISC.
  • Bratton, S.B. et al. (2001) EMBO J. 20:998. Procaspase-3 is recruited and activated following formation of the Caspase-9-containing apoptosome.
  • Han, J. et al. (2004) J. Biol. Chem. 279:22020. Granzyme B and/or Caspase-3 cleavage of Mcl-1 releases sequestered pro-apoptotic BIM and mitochondrial Cytochrome c.
  • Hsu, H. et al. (1996) Cell 84:299. The adaptor TRADD mediates interactions between TNF-α R1 and FADD.
  • Irmler, M. et al. (1997) Nature 388:190. Death receptor signals are inhibited by FLIP.
  • Korfali, N. et al. J. Biol. Chem. 279:1030. Lamin cleavage is delayed in Caspase-7-/- cells.
  • Li, H. et al. (1998) Cell 94:491. Caspase-8 cleavage of BID is downstream of Fas ligation.
  • Li, P. et al. (1997) Cell 91:479. Apaf-1/ATP/Procaspase-9/Cytochrome c and apoptosome formation.
  • Medema, J.P. et al. EMBO J. 16:2794. Caspase-8 (FLICE) activated downstream of Fas.
  • Muzio, M. et al. (1996) Cell 85:817. Caspase-8 is recruited to the Fas DISC.
  • Ricci, J.-E. et al. (2004) Cell 117:773. NDUFS1, the 75 kDa subunit of respiratory complex I is a Caspase-3 substrate.
  • Slee, E.A. et al. (2001) J. Biol. Chem. 276:7320. Lamin B is a Caspase-3 substrate.
  • Stennicke, H.R. et al. (1998) J. Biol. Chem. 273:27084. Procaspase-3 is a Caspase-8 substrate.
  • Wolf, B.B. et al. (1999) J. Biol. Chem. 274:30651. ICAD is a Caspase-3 substrate.

Apoptosis Recognition by Phagocytes Illustration

  • Fadok, V.A. et al. (1998) Cell Death Differ. 5:551. Phosphatidylserine in apoptosis recognition by phagocytes.
  • Hall, S.E. et al. (1994) J. Immunol. 153:3218. Mannose/fucose-specific lectin in apoptosis recognition.
  • Hamon, Y. et al. (2000) Nat. Cell Biol. 2:399. ABC1 involvement in membrane redistribution of phosphatidylserine.
  • Lauber, K. et al. (2004) 14:277. Review detailing mechanisms of apoptosis recognition by phagocytes.
  • Moodley, Y. et al. (2003) Am. J. Pathol. 162:771. TSP-1 bound to CD36 on the apoptotic cell is recognized by the phagocytic macrophage.

Heat Shock Proteins Illustration

  • Beere, H.M. et al. (2000) Nat. Cell Biol. 2:469. HSP70 inhibits the recruitment of Caspase-9 to the apoptosome.
  • Bruey, J.M. et al. Nat. Cell Biol. (2000) 2:645. HSP27 binds and interferes with cytosolic Cytochrome c.
  • Gurbuxani, S. et al. (2003) Oncogene 22:6669. HSP70 inhibits AIF nuclear transport.
  • Pandey, P. et al. (2000) EMBO J. 19:4310. HSP90 suppresses Cytochrome c-mediated APAF-1 oligomerization and Caspase-9 activation.

Mediators of DNA Degradation Illustration

AIF

  • Daugas, E. et al. (2000) FASEB J. 14:729. AIF translocates from the mitochondria to the nucleus during apoptosis.
  • Susin, S.A. et al. (1999) Nature 397:441. AIF causes chromatin condensation and nuclear fragmentation.

CAD/ICAD

  • Enari, M. et al. (1998) Nature 391:43. CAD is de-repressed by Caspase-3-mediated ICAD cleavage.
  • Halenbeck, R. et al. (1998) Curr. Biol. 8:537. CPAN (CAD) repression is relieved by Caspase-mediated cleavage of DFF45 (ICAD).
  • Liu, X. et al. (1997) Cell 89:175. DFF(CAD) mediates DNA degradation downstream of Caspase-3.
  • Sharif-Askari, E. et al. (2001) EMBO J. 20:3101. ICAD is a Granzyme B substrate.
  • Thomas, D.A. et al. (2000) Immunity 12:621. ICAD is a Granzyme B substrate.

Endo G

  • Li, L.Y. et al. (2001) Nature 412:95. Endo G translocates from the mitochondria to the nucleus during apoptosis and elicits DNA fragmentation.

Viral Proteins Illustration

  • Andrade, F. et al. (2001) Immunity 14:751. Viral protein L4-100 kDa inhibits Granzyme B activity.
  • Cartier, A. et al. (2003) Cell Death Differ. 10:1320. HSV protein US3 inhibits Granzyme B activity.
  • Perez, D. & E. White (2000) Mol Cell 6:53. Viral E1B 19K blocks apoptosis by inhibiting Bax.
  • Quan, L.T. et al. (1995) J. Biol. Chem. 270:10377. CrmA inhibition of Granzyme B.
  • Zhou, Q. et al. (1997) J. Biol. Chem. 272:7797. CrmA inhibition of Caspase-8.

Cytokine/Chemokine Response to Influenza Virus Illustration

  • Bussfeld, D. et al. (1998) Cell Immunol. 186:1. Influenza virus-infected cells express MIP-1α, MCP-1, and IP-10.
  • Cheung, C.Y. et al. (2002) Lancet. 360:1831. Influenza infection induces TNF-α expression.
  • Fawaz, L.M. et al. (1999) J. Immunol. 163:4473. Influenza virus induction of IL-15.
  • Julkunen, I. et al. (2001) Cytokine Growth Factor Rev. 12:171. Review highlighting influenza pathogenesis and induced cytokine expression.
  • Kawaguchi, M. et al. (2001) Clin. Exp. Allergy. 31:873. Influenza virus-infected cells express Eotaxin.
  • Matikainen, S. et al. (2000) Virology 276:138. Influenza virus-infected cells express MIP-1α, MIP-1ß, RANTES, MCP-1, MCP-3, MIP-3a, IP-10, and IL-8.
  • Matsukura, S. et al. (1996) J. Allergy Clin. Immunol. 98:1080. Influenza virus-infected cells express RANTES, IL-8, and IL-6.
  • Monteiro, J.M. et al. (1998) J Virol. 72:4825. Influenza virus induction of IL-12.
  • Pirhonen, J. et al. (1999) J. Immunol. 162:7322. Influenza virus induces IL-1β production.
  • Sareneva, T. et al. (1998) J. Immunol. 160:6032. Influenza A virus-infected cells express IFN-α/ß and IL-18 and synergistically enhance IFN-? expression in T cells.
  • Sprenger, H. et al. (1996) J. Exp. Med. 184:1191. Influenza virus-infected cells express MIP-1α, MCP-1, and RANTES.
  • Tong, H.H. et al. (2003) Infect. Immun. 71:4289. Influenza virus-infected cells express TNF-a and IL-6.
  • Topham D.J. et al. (1997) J. Immunol. 159:5197. CTLs use Fas and/or Perforin-dependent mechanisms in defense of influenza virus.





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