=====APPENDIXA=====

USEFUL INTERNET ADDRESSES

Six years ago, Walter Gilbert urged that scientists "hook our individual computers into the worldwide network that gives us access to daily changes in the databases and also makes

immediate our communications with each other:'l The Internet expands constantly and with it the wealth of information; today's scientists can hardly do without it. New and addi­tional data come up every day-not to speak of the daily communication processes over the net. Many data found in the present book were retrieved from various www addresses (see below) and subsequently collected in order to offer a specific and comprehensive compila­tion of data relating to the structure and function of MHC molecules. As the present data will continuously be updated, we have listed below some helpful addresses which we think may serve the molecular biologist's and immunologist's interests.

WWW Entrez: http://www.ncbi.nlm.nih.gov This network browser is provided by the National Center for Biotechnology Information and allows searching and browsing of protein and nucleic acid databases, as well as related references from MEDLINE.

DBGET: http://www.genome.ad.jp/dbget/: This is a database retrieval system and allows retrieval of related entries in different data­bases such as GenBank, EMBL, SWISS-PROT, PIR etc.

Pedro's Biomolecular Research Tools: http://www.public.iastate.edu/-pedro/research_tools.htmI.This is an outstanding collec­tion ofWWW links to services useful for molecular biologists. It comprises a list of molecu­lar biology database search and analysis facilities, and bibliographies.

SEQUENCE DATABASES

EMBL: http://www.ebi.ac.ukIebLdocs/embCdb/ebi/topembl.html GENBANK: http://www.ncbi.nlm.nih.gov/Genbankiindex.html GSDB:http://www.ncgr.org/gsdb/gsdb.html PIR:http://www.gdb.org/Dan/proteins/pir.html SWISS-PROT: http://www.ebi.ac.uk!ebLdocs/swiss-proCdb/swisshome.html

MHC RESOURCES

http://www.uni-tuebingen.de/unilkxi/: Our own homepage provides access to MHC ligands and peptide motifs.

http://www.icnet.ukIaxp/tiaiindex.html: This page provides links to resources available from the Tissue Antigen Laboratory at the

Imperial Cancer Research Fund. Included are HLA sequence data, HLA nomenclature in­cluding monthly updates.

450 MHC Ligands and Peptide Motifs

http://histo.cryst.bbk.ac. uk: Histo is dedicated to the investigation of the relationship between sequence, structure

and function of the proteins of the MHC. There are also collections of mouse class II se­quences and non human and non mouse sequences.

http://www.hgmp.mrc.ac.uk: This is a database of the human MHC and contains eDNA sequences of all current

alleles as well as physical maps.2

http://wehi.wehi.edu.au/mhcpep/ : Database of Major Histocompatibility Complex binding pep tides at the Walter and Eliza

Hall Institute-Melbourne, Australia.

http://www3.ncbi.nlm.nih.gov: This access is provided by the National Center for Biotechnology Information and offers

gene maps of the human genome as well as human/mouse homology map.

http://www.swmed.edu/home_pages/ASHIIashi.htm: This is organized by the American Society for Histocompatibility and Immunogenetics

and offers access to HLA sequence alignments.

http://hiv-web.lanl.gov/immuno: HIV Molecular Immunology Database. Offers T cell epitope maps on HIV proteins,

alignments, and annotation, as well as a summary and map of linear B cell epitopes and monoclonal antibodies.

REFERENCES I. Gilbert W. Towards a paradigm shift in biology. Nature 1991; 349:99. 2. Newell WR, Trowsdale 1, Beck S. MHCDB: database of the human MHC (release 2). Im­

munogenetics 1996; 45:6-8.

===== APPENDIX B=====

COMPUTER PROGRAMS ARE AVAILABLE FROM THE FOLLOWING SOURCES:

Joe D'Amaro Department of Immunohematology and Blood Bank University Hospital Leiden PO Box 9600 2300 RD Leiden The Netherlands

Miles Davenport Molecular Immunology Group Institute of Molecular Medicine Nuffield Department of Medicine University of Oxford John Radcliffe Hospital Headington, OX3 9DU United Kingdom

Burkhard Fleckenstein NMI (Naturwissenschaftliches und Medizinisches Institut an der Universitat Tiibingen in Reutlingen) Eberhardstr. 29 72762 Reutlingen Germany

Jiirgen Hammer Roche Milano Ricerche Via Olgettina 58 20132 Milano Italy

=====APPENDIX C=====

ABBREVIATIONS

4F2 AA ACh Ag APC B. polymyxa ~2m BAGE Bf ~-gal BHRF BIP BLAST-l BSA BST-2 BZLFI C. cAg CArG CD CDK4wt CKS-2 CKShsl CLIP cM c-myc COl CRE CRY CSFV CSP CYP21 Derp E. coli EI-E7 EBNA EBV

lymphocyte activation antigen 4F2 amino acids acetylcholine antigen adenomatous polyposis coli protein Bacillus polymyxa ~2-micro globulin tumor antigen factor B ~-galactosidase Epstein-Barr virus bel-2 homologue bone inducing protein B-lymphocyte activation marker bovine serum albumin bone marrow stromal cell membrane protein Epstein-Barr virus trans-activator protein Caenorhabditis spec. core antigen mouse CArG-binding factor A cluster of differentiation cyeline dependent kinase cylcine dependent kinase subunit 2 cyeline-dependent kinases regulatory subunit 1 class II associated invariant chain peptide centiMorgans proto-oncogene cytochrome c oxidase polypeptide I cAMP response element Cryptomeria japonica major allergen classical swine fever virus circumsporozoite protein steroid 21-hydroxylase Dermatophagoides pteronyssinus Escherichia coli immediate early protein Epstein-Barr virus nuclear antigen Epstein-Barr-virus

454

elFC env EqMb ER ER60 ERP72 Fc FLU Fr GAD gag GAGE GBLP gp gplOO GPIX HA HBBCP HCV HEL HER-2 HER-2/neu HFPS HGNBP HIV HLA hnRNP HPV HSI HSC HSHM HSP HSrn HSV HTLV ICAM ICP-27 ICS IDDM IE IEF IFN Ig IgVH Ig-SF Ii IL Int-6

IP IRBP

protein translation factor envelope equine myoglobin endoplasmic reticulum

MHC Ligands and Peptide Motifs

endoplasmic reticulum resident protein endoplasmic reticulum resident protein fragment cystallizable Influenza fraction glutamic acid decarboxylase group-specific antigen tumor antigen guanine nucleotide binding protein ~ subunit-like protein gylcoprotein ->pmel platelet glycoprotein IX (syn.: CD42A) hemagglutimin human cytomegalovirus Hepatitis B virus hen egg lysozyme proto-oncogene ->HER-2 human fasyl pyrophosphate synthetase human nucleotide binding protein human immunodeficiency virus human lymphocyte antigen heterogenous ribonucleoprotein human papilloma virus hematopoietic lineage cell specific protein heat shock protein constitutive human expressed sequence tag heat shock protein human C6.1A protein (proto-oncogene) Herpes simplex virus Human T-lymphotrophic virus intercellular adhesion molecule HSV infected cell protein (transciptional regulator IE63) IFN consensus sequence insulin dependent diabetes mellitus immediate early human retinoblastoma binding protein P48 interferon immunoglobulin immunoglobulin variable region of heavy chain immunoglobulin super family invariant chain interleukin a highly conserved, widely expressed gene, which is mutated by mouse mammary tumor virus in mammary preneoplasia prostacyclin receptor gene interphotoreceptor retinoid-binding protein

Appendix C

IRS JAK1 JHMV kb kD K-ras L. LAR LCMV LDH LDL lemA LIF LLO Imp-1 Imp-2 ImrA Lol P LSA-1 Ly M. MAGE MART-1 MBP Mbp MCC MCMV mdm Melan/MART -1 MET MHV MIF miHAg MMTV MOG MoHb MoMb MP MuLV MUM-1 MUT MV nef NK NKAT NP NRE NS OGDH ORF OVA

IFN response sequence Janus kinase JHM strain of mouse hepatitus virus kilo base pairs kilo-Dalton Kirsten -ras Listeria spec. leucocyte antigen related lymphocytic choriomeningitis virus lactate dehydrogenase low density lipoprotein putative regulator protein in L.monocytogenes leukemia inhibitory factor listeriolysin 0 latent membrane protein 1 latent membrane protein 2 lincomycin resistance protein from S. lincolnensis Lolium perenne liver-stage antigen-1 lymphocyte antigen Mycobacterium spec. melanoma associated antigen melanoma antigen myelin basic protein megabase pairs moth cytochrome c murine cytomegalovirus tumor antigen ->Mart-1 oncogene mouse hepatitis virus migration inhibitory factor minor histocompatibility antigen murine mammory tumor virus myelin oligodendrocyte glycoprotein mouse hemoglobin mouse myoglobin matrix protein murine leukemia virus tumor antigen tumor antigen measles virus negative factor natural killer natural killer associated transcript nucleoprotein negative response element nonstructural proteins oxoglutarate dehydrogenase open reading frame ovalbumin

455

456

P. PI-CDC2I p2CA PA2S PAI-I PBI PCC PGAL PGSG PKM-2 PLP pmel pol pp PR PRAI-SCS

pree. preS RAGE ras RBAP-2 rep RSV RT s. lincolnensis sAg SEC6I SFV SIV SLE SMCY

SNase SSP2 SSR STARP Substance P SV SWM SWMb T TAP tax TCR TCRV TF Tf TIMP-I TIMP-2 TIS

MHC Ligands and Peptide Motifs

Plasmodium spee. human CDC2I homolog (chromatin binding protein) murine alpha-ketoglutarate dehydrogenase homologue 20S proteasome regulator (syn.: lIS regulator) plasminogen activator inhibitor-I RNA-directed RNA polymerase subunit PI pigeon cytochrome c phosphoglyceraldehyde platelet proteolycan core protein pyruvate kinase MI (muscle) isoenzyme proteolipid protein melanoma antigen (syn.: gp 100) polymerase phosphoprotein Puerto Rico yeast phospho ribosyl aminomidazole

succinocarboxamide cynthase precursor Hepatitis B virus S antigen precursos tumor antigen proto-oncogene retinoblastoma associated protein 2 regulator of replication and gene expression respiratory syncytial virus reverse transcriptase Streptomyces lincolnensis soluble antigen endoplasmic reticulum peptide exporter Semliki Forest virus simian immunodeficiency virus systemic lupus erythematosus male-specific transplantation antigen (ubiquitously transcribed

teratricopeptide repeat gene on the Y chromosome) Staphylococcal nuclease sporozoite S protein 2 signal sequence receptor sporozoite threonine and asparagine rich protein neuropeptide Sendai virus ->SWMb sperm whale myoglobin T-antigen transporter associated with antigen processing HTLV-I derived trans-activator T cell receptor T cell-receptor variable segment transcription factor transferrin tissue inhibitor of metalloproteinase 1 tissue inhibitor of metalloproteinase 2 EGF-response factor 1

Appendix C

TNF TRAP TRP-2 UBC UC UL-18 VLA YOP ysa-l miHAg UL

tumor necrosis factor thrombospondin related anonymous protein tyrosinase related protein ubiquitin conjugating enzyme unrelated chromatin HCMV gene encoding a class I heavy chain homologue adhesion receptor Yersinia outer membrane protein yeast protein (Saccharomyces cerevisiae) minor histocompatibility antigen viral gene locus

457

===========INDEX=========== 205 proteasome 5, 6, 228, 229 265 complex 228 3'UT region 22

A

a-chain 7,23 a-helical 3, 141 al and [31 domains 5,22,143 a[3 T cell 372 agonist 24 alignment 3,219,220-226 allele-specific peptide motifs 3, 8 alleles 5,8, 18,19,22,23,25-28,30,218,

220,225,382,383 allograft rejection 2 alloreactive T cells 373,374 alloreactivity 373,374,381 allorestricted T cells 374 aminopeptidase N 8 anchor 7, 141-143,218-227,230 anchor amino acids 218,219,223,226 anchor position 218-225 anchor residues 143,218-227 anchor-pocket interactions 141 anchors 218-222,225,226,232 anergy 372,381, 382 antagonist 25,372 antibodies 1-3,375,377-379,383,450 antigen processing 5,6,9,24,227-229,

231 antigen-presenting 3,7-9,17,24,231,

372,381-383 APC 17,372,381 ATP-binding cassette (ABC) transporter

loci 24 autoimmune disease 8,9, 17,23,25,26,

382,383 autoimmunity tolerance 382 auxiliary 219-222,225,226 auxiliary anchors 219-222,225,226

B

B cell 2,4,9,23,24,232,373,378,381, 450

B lymphocyte 231 [3-chain 7, 23, 143

[32-microglobulin 5,23,28,142,220, 230,231

bacterial infection 381 Bf 25 BiP 232

c C-terminal 27,142,143,218,219,221,

224,226,227,230 C-terminus 6, 141,230 C2 17,25,26 C4 17,25,26 calnexin 6,230, 232 calreticulin 6, 230, 231 CAT genes 20 cathepsin D 8, 232 cathepsins 9,232 CDl 28 CD13 8 CD4+ Thl 372,373 CD4+ Th2 372,373 CD8+ 7,9, 17, 18, 372, 373, 381, 383 CD8+ T cells 7,9, 18,373,381 CDR 142 cell-mediated immunity 381 chaperone 5-7,230-232,381 chromosome 6 4,5, 17,23,27,28,30,31 cis-/trans-acting factors 21 class I 3-9,17-24,26-31,50,141-143,

217-223,227,229-231,371-373,375, 377

class I groove 5,30 class I ligand 3, 5, 6, 220, 229 class II 3-5,7-9,17-19,21-26,28-31,

143,217-219,221,222,227,231,232, 372,373,383

class II groove 8,232 class II molecules 3-9,17,21, 23-25, 30,

143,218,219,221,231,232,372,373 class II motifs 3, 4 class III 18,25,29-31 class III region 18, 25 classical HLA class I loci 18 CLIP 8,232 clonal anergy 382 clonal deletion 372, 382 co-stimulatory interactions 372 Collla2 30

460

contact sites 141,219 costimulation 372 costimulatory ligands 372 CRE 21,25 crystal structures 4 crystallization 3 CYP21 18,26 cytoplasmic domain 19-22,372 cytosol 5,6,9,228,230,231 cytotoxic T lymphocyte 4

D

debris 381 degenerate 143,219,221,227 degradation 5,9,27,218-221,227,228,

231,232 deletion 23,26,372,381,382 dendritic cell 4,7,9,24,231,381,383 determinant selection 3 differentiation antigen 378,383 D~ 5,8,23,25 DMB 5, 8, 23, 25 DP 17, 18,21-23,25,28-30 DP subregion 22,23 DPA 5,23,68 DPB 23 DQ 17,18,21-23,25,29,30 DQ subregion 22 DQA 22,30 DR 17,18,21,22,25,26,28,29 DR molecules 143 DR subregion 22 DRI 143 DRA 5,18,22,29,30 DRBI 5,22,25,73 dw-3 29

E

elution 3 endopeptidases 232 endoplasmic reticulum 5,18,27,217,367 ER lumen 230,231 exogenous antigen 9,231,232 exon-intron organization 19 exopeptidases 8,232 expression of class II genes 24

F

foreign antigen 3,19,372,382 foreign MHC 8,373-375 fragments 3,5,229,232,381

MHC Ligands and Peptide Motifs

fragments of antigen 3 frameshift mutation 20, 23, 383 ft 29 fusion protein 383

G

yo T cell 371,372 genomic organization 17,20,21,26,28 germ line 373 GNLl 20 gp966,9,231,381 graft-versus-Ieukemia 374 grc-G/C 29 groove 4-8,22,30,141-143,221,232,373

H

H-2 1,2,4,141,142,371,375,376,377 H2-D 19 H2-K 19,29 H2-Q 29 H2-T 29 H2RIIBP 21 HC/~2m complex 230 helper T lymphocyte 4 HLA 2,4,6-8 HLA association 382 HLA class II region 17,21 HLA matching 374 HLA-A 4,7,17-19,141,142,218-220,

223,225,226,230 HLA-B 5,6,7, 18-20,26,27,141,142,

218-220,230 HLA-C 4, 18, 19,230 HLA-DM 23,25,30 HLA-DN 4,22,23 HLA-DO 23 HLA-E 4, 19,20 HLA-F 4, 19,20 HLA-G 4,19,20 HLA-H 19,20 HLA-J 19 HLA-X 19 Hsc70 6,230 HSP70 26,27 HSRI 20

I

IFNy 6,9,21,24,25,229,373 Immune response (Ir) genes 2 immunoglobulin domains 4 infectious agent 381

Index

intermediate of processing 229 International Histocompatibility

Workshops 2 invariant chain 7,8,25,232 ITAM motif 372

K

KE630

L

LCMV 2 leitcytokines 373 length 3,5,6,22,24,141,143,217-221,

223,226,228,229 LMP2 5,6,24,29,228,229 LMP75,6,24,30,228,229 locus 5,17-20,22-24,26,27,29-31 low affinity 3, 382 lumen 5,24,228,230,231 Ly49 371 lymphotoxin 27

M

macrophage 3,4,9,24,27,231,373,381 MAGEl 383 major histocompatibility complex

(MHC) 1,4,17,30 malaria 19 male-specific peptides 381 Max-Planck-Institut fur Biologie 2 MECLl 6, 228, 229 melanomas 7 MHC 1-9,17,19-21,23-25,27,28,30,

141-143,217-232,371-375,379-383 MHC class I 3-7,9,17,19-21,24,28,30,

31,141, 217-223, 227, 229, 230,372, 375,383

MHC class I unrelated loci 20 MHC class II 4,5,7-9,17,23-25,30,31,

143,219,221,227,231,232 MHC class II transactivators 23 MHC function 2,3 MHC genes 1,2,5,17,20,21,31 MHC I assembly 231 MHC I molecules 141, 219, 225, 226,

230,231,373,381 MHC II peptide motifs 220,221 MHC molecules 2-4,6,7,9,17,19,21,

142,217-220,222-224,228,230,231, 371,373,374,381

MHC motif 231,382,383 MHC polymorphism 7,8,28,373 MHC Related Loci 20 MHC restriction 2,3,374 MHC-peptide complex 222,372 MICA 20 MICB 20 MIlC 8,217, 232

461

minor histocompatibility antigen 231,381 missing self 371 mixed lymphocyte reaction 2 MOG 20 motif tables 220-222

N

Nand C termini 5, 141 N-terminus 141, 142 natural killer cells 371 natural ligands 143,219,220,222-226,

381 natural MHC ligand 382 negative regulatory element 21 NK cell 27,37l NKATl 371 NKAT4371 nomenclature 18,22,449 nonamers 3,7,218,223,225,226,227 nonclassical HLA class I loci 19 number of alleles 19,22

o oncogene 7,378,383 OTF3 20

p

P2 pocket 142 PA28 regulator 6,229 PAP program 224, 225, 227 patterns 2,28,222-227,377 peptide acceptor 6, 9, 231 peptide binding 19,22,28,141, 143,

217,220 peptide libraries 4,219,221,227 peptide ligands 3, 8 peptide motifs 3,7,8,142,217-224,226,

227,382 peptide-binding groove 5,8,141,143 peptide-binding regions (PBR) 19 peptide-dependent 371,374

462

pep tides 3-9,18,20,23,24,30, 141-143, 217-232,372-374,381-383

perf orin 373 phagocytosis 8, 9, 232 pocket specificity 8, 142 pockets 5,7,8,141-143,221,383 polymorphism 5,7,8,17,19,20-23,25,

28-30,141,143,230,373,383 positive selection 3,373 post-translational 21 prediction 143,220,222-227,383 prediction of MH C ligand 7 preferred residues 142,219-221,225-226 processing motif 221 processing steps 229 promotor sequences 21 proteasome 5,6,9,24,27,228-230 protein disulfide isomerase 6, 231 protein isolation 3 pseudogenes 19,22, 23

R

RA-inducing peptide 383 rcc 29 RD 27 reaction 2,24,25,373,374,381 receptor-mediated uptake 232 refined motifs 223 regulation ofMHC class I expression 21 regulatory elements 21 rheumatoid arthritis 382 RINGI 29,30 RING2 30 RING3 24,29,30 RTl.A 29,30 RXRB 30

s self peptide 142 self reactive T cells 372 self tolerance 372,374,375,382 side chain scanning 227 stress signal 9 superantigens 381 synthetic peptides 3,219,220,223,228,

382,383

T

T cell activation 372

MHC Ligands and Peptide Motifs

T cell epitopes 7,220-227,381-383 T cell receptor 3,7,142,222,372,373,

376,381 T cell receptor genes 3 TAP 5,6,9,21,24,374 TAPI 24, 30, 230 TAP224,29,30,230 tapasin 6, 230 TCR 3, 142, 143,222,372,373 TCR diversity 373 TCR-peptide 143,222 threonine protease 5 thymic epithelial cells 231, 232 tissue specific cytotoxic T -cells 375 TNFA 26,27 TNFB 26,27 trans-species hypothesis of evolution 19 transmembrane region 4,5,18, 19,21 transplantation 1,29,225,373,374,377,

381 trimolecular complex 3 tumor antigen 378,383 tumor immunology 378,380,383 tumor-associated antigen 374,383 tumor-suppressor gene 383 tyrosinase 7,345,383

u ubiquitin 228 unfavorable residues 220, 225, 226, 232 unrelated chromatin 17 untranslated (UT) sequence 19

v vaccines 4, 9 viral 6,31,228,229,231,371,377,

381,383 viral antigen 229,381,383 viral particles 381 virus infection 7,373 virus-infected cell 4,382 virus-specific CTL 3

x X box 25 X-ray crystallography 3,142

z ZNF173 20