Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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L. J. and Knuth, A. (2000) Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HAL)-DRB4*0101±0103 and recognized by CD4 + T lymphomcates of patients with NY-ESO-1-expressing melanoma. J. Exp. Med., 191, 625±630. 28 Ayyoub, M., Stefanovic, S., Servis, C., Sahin, U., Guillaume, P., Rimoldi, D., Rubio-Gody,V.,Valmori, D., Romero, P., Cerottini, J.-C., Rammensee, H.-G., Pfreundschuh, M., Levy, F. and Speiser, D. (2002) Protesasome-assisted identification of a SSX-2 derived epitope recognized by tumor reactive cytllytic T lymphocytes infiltrating metastatic melanoma. J. Immunol., in press. References 29 Old, L. J. and Chen,Y. T. (1998) New paths in human cancer serology. J. Exp. Med., 187, 1163±1167. 30 Hofbauer, G. F., Schaefer, C., Noppen, C., Boni, R., Kamarashev, J., Nestle, F. O., Spagnoli, G. C. and Dummer, R. (1997) MAGE-3 immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. Am. J. Pathol., 151, 1549±53. 31 Jungbluth, A. A., Chen,Y. T., Stockert, E., Busam, K. J., Kolb, D., Iversen, K.,Williamson, B., Altkori, N. and Old, L. J. (2001): Immunohistochemical analysis of NY-ESO-1 antigen expressed in normal and malignant tissues. Int. J. Cancer, 92, 856±860. 29
30 Cancer Immune Therapie: Current and Future Strategies Edited by G. Stuhler and P. Walden Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5 (Electronic) 3 Processing and Presentation of Tumor-associated Antigens Peter-M. Kloetzel and Alice Sijts 3.1 The Major Histocompatibility Complex (MHC) Class I Antigen-Processing Pathway As part of the vertebrate immune surveillance system cytotoxic T cells recognize antigens which are bound by MHC class I proteins. To allow binding to MHC class I molecules a protein has to be proteolytically processed to peptides. The recognition of the MHC±peptide complex on the plasma membrane by a T cell receptor (TCR) which is specific for a given antigenic peptide bound to a specific MHC class I molecule eventually leads to T cell activation [1]. Considering the complexity of the MHC class I sequence motifs, any proteolytic system involved in the generation of immuno-dominant MHC class I epitopes has to be able to produce peptides of the appropriate size (8±10 residues) and amino acid sequence diversity, and it has to be able to generate peptides with defined C-terminal anchor residues in sufficient efficiency from a large variety of different proteins in the cytosol and nucleus. Today it is widely accepted that the proteasome system is responsible for the generation of the majority MHC class I ligands [2±4]. The proteasome is the major cytosolic protease complex in eukaryotic cells. It is composed of a proteolytically active core, i.e. the 20S proteasome and two 19S regulator complexes which attach to both sides of the barrel-shaped 20S proteasome. The complex formed by the cylinder-shaped 20S proteasome and the two regulators is called the 26S proteasome. The 20S proteasome consists of 14 non-identical subunits ranging in molecular weight from 31 to 21 kDa and is composed of four stacked rings of seven subunits each. The seven different a subunits form the two outer rings, while the two inner rings are formed by the seven different b subunits [3]. The proteolytically active sites are restricted to the lumen of the cylinder and are formed by three of the seven b subunits, i. e. subunits d (b1), Z (b2) and MB1 (b5). In total, the 20S proteasome therefore possesses six active sites within the two inner b rings [5, 6]. Proteasome function can be modulated through the interaction with several regulatory proteins and in order to enter the catalytic chamber protein substrates have to be in an unfolded or extended conformation [7, 8]. Unfolding of substrates is thought to be performed by the six ATPases of the 19S regulator complex which directly attach to the 20S proteasome and form the so-called base structure of the 19S regulator.
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Cancer Immune Therapie: Current and
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Editors: Dr. Gernot Stuhler Univers
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VI Preface Recent years have seen a
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VIII Contents 2.5.3 Antigens Encode
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X Contents 6.4.2 Natural Killer (NK
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XII Contents 9.6 Loading DC with An
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XIV Contents 14.2.2.1 Cancer-specif
Page 15 and 16: List of Contributors Richard Bucala
Page 17 and 18: Color Plates Fig. 5.2 The MHC class
Page 19 and 20: Fig. 5.5 Different immune effector
Page 21 and 22: Fig. 5.17 Possible pathway for the
Page 23 and 24: Fig. 6.2 T lymphocytes in the tumor
Page 25 and 26: Index a acidic and basic fibroblast
Page 27 and 28: ±, see also tumors cationic lipids
Page 29 and 30: e EBV see Epstein-Barr virus EDR se
Page 31 and 32: immature Mo-DCs 184 immune cells ±
Page 33 and 34: MHC class I antigen-processing mach
Page 35 and 36: ±, onco- 209 ±, over-expressed ce
Page 37 and 38: TICD see tumor-induced cell death T
Page 39 and 40: Part 1 Tumor Antigenicity Cancer Im
Page 41 and 42: 4 1 Search for Universal Tumor-Asso
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Page 55 and 56: 18 2 Serological Determinants On Tu
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Page 69 and 70: 32 3 Processing and Presentation of
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Page 79 and 80: 42 4 T Cells In Tumor Immunity cult
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Page 87 and 88: 50 4 T Cells In Tumor Immunity Tab.
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Page 91 and 92: 54 4 T Cells In Tumor Immunity 53 T
Page 93 and 94: Part 2 Immune Evasion and Suppressi
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82 5 Major Histocompatibility Compl
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96 6 Immune Cells in the Tumor Micr
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98 6 Immune Cells in the Tumor Micr
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100 6 Immune Cells in the Tumor Mic
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Tab. 7.1 Effects of tumor-derived m
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122 7 Immunosuppresive Factors in C
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156 8 Interleukin-10 in Cancer Immu
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Part 3 Strategies for Cancer Immuno
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180 9 Dendritic Cells and Cancer: P
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204 Cancer Immune Therapie: Current
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206 10 The Immune System in Cancer:
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232 11 Hybrid Cell Vaccination for
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254 12 Principles and Strategies Em
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270 13 Applications of CpG Motifs f
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288 14 The T-Body Approach: Towards
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300 15 Bone Marrow Transplantation
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312 16 Immunocytokines: Versatile M
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348 17 Immunotoxins and Recombinant
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382 Glossary tion to the variable d
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384 Glossary suppressor gene produc
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386 Glossary press the proper recep
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388 Glossary gp96 See Chaperone. Gr
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390 Glossary cytes and addressing l
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392 Glossary T bodies are being tes
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