Target Discovery and Validation Reviews and Protocols

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Overview of Immune System 295 Fig. 9. Schematic of class II pathway of antigen processing. The invariant chain transports the major histocompatability complex (MHC) class II molecules from the endoplasmic reticulum to a specialized endosomal compartment where the invariant chain is cleaved leaving a small peptide CLIP. Exogenous antigens that are taken up by endocytosis are cleaved into small peptide fragments within the endosomes. Within the endosomes, the CLIP fragment is eventually replaced by the cleaved peptides and then complexes are delivered to the cell surface. CPL, compartment for peptide loading. peptides are generated by the proteasomes, multicatalytic protease assemblies that are responsible for the major pathway of protein turnover in the cytoplasm (38). The peptides generated by the proteasome are subsequently translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen presentation (TAP) heterodimer, which may display a certain degree of specificity by selecting peptides with length and termini optimal for the class I binding (39). The binding between the peptide and class I molecule takes place inside the ER. Tumor cells therefore present peptides from tumor antigens in the context of class I MHC to CD8+ T-cells. 6.2. Class II Pathway of Antigen Processing Class II molecules are present only on the surface of specialized APCs, including DCs, B-cells, and macrophages. These are predominantly loaded with peptides derived from exogenous proteins that enter the endocytic pathway of
296 Sioud Fig. 10. Critical molecules involved in the interaction between the T-cells and the antigen-presenting cells. The first signal consists of the T-cell receptor (TCR)–peptide– MHC interaction. The second co-stimulatory signal resulting from the interaction between CD28 and B7 molecules, leading to the amplification of the signaling process in naive T-cells and protects activated cells from death. In absence of signal 2, T-cell activation will lead to anergy. Several inducible costimulatory molecules, in particular CTLA4, negatively modulate activation of T-cells. Notably, all of the constitutively expressed co-stimulators have positive amplifying effects, whereas the group of inducible costimulators contains positive (e.g., inducible co-stimulatory [ICOS]) and negative (e.g., CTL4 and PD-1) regulators. APC, antigen-presenting cell.
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METHODS IN MOLECULAR BIOLOGY 360 T
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M E T H O D S I N M O L E C U L A R
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© 2007 Humana Press Inc. 999 River
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vi Preface get. Approaches to targe
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viii Contents 10 Transgenic Animal
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x Contributors SAHOHIME MATSUMOTO
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xii Contents of Volume 2 12 Validat
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2 Sioud disease pathogenesis and pe
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4 Sioud A more fruitful approach fo
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6 Sioud both transient and permanen
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8 Sioud serum biomarkers. This syne
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10 Sioud Fig. 2. Schematic of targe
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12 Sioud 13. Magin, T. M. (1998) Le
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Harnessing the Human Genome 15 The
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Harnessing the Human Genome 17 Fig.
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Harnessing the Human Genome 23 The
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Harnessing the Human Genome 27 repr
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Harnessing the Human Genome 29 14.
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Harnessing the Human Genome 31 45.
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34 Imoto et al. (4,5), and Bayesian
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36 Imoto et al. 2. Materials Two ty
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38 Imoto et al. Fig. 3. Graphical v
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40 Imoto et al. Fig. 5. Result of t
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42 Imoto et al. p(D |G) = ∫ p(D,
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44 Imoto et al. β k (k = 1,…,q j
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46 Imoto et al. Fig. 7. Partial res
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48 Imoto et al. Fig. 8. Strategy to
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50 Imoto et al. Fig. 9. (continued)
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52 Imoto et al. Table 3 List of Roo
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54 Imoto et al. 5. De Hoon, M. J. L
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56 Imoto et al. 39. Kamimura, T., S
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58 Beaty et al. cytotoxic drugs and
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60 Beaty et al. Fig. 1. Principles
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62 Beaty et al. oligonucleotide mic
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64 Beaty et al. 3. The 12% polyacry
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66 Beaty et al. 2.3.3. Protein Stai
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68 Beaty et al. 3.1.3. Labeling of
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70 Beaty et al. 1 µL of the anneal
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78 Beaty et al. using a protein ass
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82 Beaty et al. Fig. 2. Preparation
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84 Beaty et al. search in. A widely
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86 Beaty et al. 3. Kern, S. E., Hru
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88 Beaty et al. 34. Peters, D. G.,
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5 Molecular Classification of Breas
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Molecular Profiling of Breast Cance
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Fig. 2. (Continued) the right ident
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6 Discovery of Differentially Expre
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Gene Target Discovery 117 In the fi
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Gene Target Discovery 119 sequences
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Gene Target Discovery 121 There is
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Gene Target Discovery 123 digestion
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Gene Target Discovery 125 Fig. 1. P
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Gene Target Discovery 127 5. Sargen
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Gene Target Discovery 129 41. Berry
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132 Matsumoto, Miyagishi, and Taira
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144 Fig. 1. The ribozyme-expression
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146 Sano and Taira 5. 10X L (low-sa
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148 Sano and Taira ribozymes may cl
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150 Fig. 3. A system for the identi
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152 Sano and Taira 4. Notes 1. We r
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9 Production of siRNA- and cDNA-Tra
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Transfected Cell Arrays 157 Fig. 1.
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Transfected Cell Arrays 159 2. The
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Transfected Cell Arrays 161 5. Simp
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164 Houdebine Fig. 1. Different met
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166 Houdebine concentrations become
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168 Houdebine Fig. 2. Major methods
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170 Houdebine integrate into the me
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172 Houdebine 2.2.3. Knock-In Into
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174 Houdebine as insulators. The co
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176 Houdebine Fig. 5. Different met
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178 Houdebine systems. Moreover, st
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184 Houdebine more extensively. Tra
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186 Houdebine and stroma. Several o
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188 Houdebine explained at the mole
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190 Houdebine of the intestinal epi
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198 Houdebine 86. Carmichael, G. G.
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200 Houdebine 121. Pailhoux, E., Vi
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202 Houdebine 156. Auerbach, A. B.,
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204 Vijayaraj, Söhl, and Magin 1.
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242 Table 3 Time Schedule For Aggre
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Page 332 and 333: 15 Potential Target Antigens for Im
Page 334 and 335: Tumor Antigen Discovery 321 develop
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Page 340 and 341: 16 Identification of Tumor Antigens
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Protein Arrays 345 18. Cekaite, H.
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Protein Arrays 347 49. Yuko Kawahas
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Index 349 Index A Acetyl-CoA carbox
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Index 351 conditional by using FRT
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Index 353 Recombinant tumor antigen
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