Processing and Presentation of Antigens brings together the views of immunologists, biochemists, cell biologists, and virologists who have a common interest in the early phases of the immune response. Antigen processing and presentation comprise a series of events that are much more complex and sophisticated than had been thought for a long time, and constitute an essential part of the biology of the immune response to T-dependent protein antigens. The book is organized into seven parts. Part I discusses the major advances and insights in antigen processing, some results on the interaction of antigen with class II MHC molecules, and the precise mechanism involved in antigen processing. Part II presents papers on endosomes, lysosomes, and recycling. Part III deals with studies on presentation in the context of class I MHC molecules. The chapters in Part IV examine interactions of antigens with class II MHC molecules. Part V contains papers on macrophages and dendritic cells as accessory cells. Part VI examines antigen presentation by B cells. Part VII covers studies on T cells.

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

One of the few volumes dedicated to antigen processing, this unique text is not only especially current but also valuable for its description of petentially "hot" areas with its "Future Directions" sections. * Current, important topics covered by this text include: Processing and presentation of foreign and self protein antigens to T lymphocytes Intracellular assembley and transport of MHC proteins Regulation of the assembley and expression of processed antigen-MHC complexes

This work is a natural history of the major histocompatibility complex written for anyone who is working on the MHC but wants to step back and review the complex in its entirety; for anyone who wants to be introduced to the MHC; or for anyone who is just curious about this much talked-about chromosomal region. By natural history is meant an all encompassing treatment of the MHC, both human and mouse, in its entire range and its details - but presented in a way that anybody can understand without consulting a variety of other sources. Most of the details are summarized in the form of tables whereas the text concentrates on generalizations and discussions. Thus, the book will be of interest to immunologists and geneticists seeking an overview of the subject and to graduate students in these disciplines. It will also be of value to technicians working in HLA-typing laboratories.

In recent years, powered by evolving technologies and experimental design, studies have better illuminated the regulating role of proteolytic enzymes across human development and pathologies. Proteolytic Signaling in Health and Disease provides an in-depth discussion of fundamental physiological and developmental processes regulated by proteases, from protein turnover and autophagy to antigen processing and presentation and major histocompatibility complex (MHC) molecules. Moving on from basic biology, international chapter authors examine a range of pathological conditions associated with proteolysis, including inflammation, wound healing, and cancer. Later chapters discuss the newly discovered network of connected events among proteases (and their inhibitors), the so-called 'protease web', and how best to study it. This book also empowers new research with up-to-date analytical methods and step-by-step protocols for studying proteolytic signaling events. - Examines biological events triggered by proteolytic enzyme activity across human development and pathologies - Discusses the role of proteolytic signaling in inflammation, wound healing, and cancer, among other disease types - Features methods and protocols supporting further study of proteolytic signaling events - Includes chapter contributions from international leaders in the field

TheBlymphocytelineagerepresentsaleadingsystemforexploring- lecularmechanismsthatunderliecellfatespecification, differentiationand cellular activation. In the past five years major advances have been achievedintheanalysisofearlyBcelldevelopment, AIDdependentclass switchrecombinationaswellassomatichypermutationandBlimp-1re- latedplasmacelldifferentiation. Manyofthesefindingsandtheirimpli- tionsarecoveredinthisvolume. Twoemergentareasofresearchthatare includedinthecontributionsfocusonthepre-BCRandIkaros-familyp- teins. Thepre-BCRisanunusualmoleculardevicethatisusedtoexecute acriticaldevelopmentalcheckpointintheBlineage. Itsmechanismof- tion in relationto the pre-TCR and the mature antigen receptors (BCR, TCR)isofconsiderableinterest. Ikaros-familyproteinsappeartofunction viarecruitingtargetgenestodomainsofcentromericheterochromatinin the nucleus. Initially discovered in lymphocytes, they represent a novel system of gene regulationvia nuclearcompartmentalization. Finally, the volumeincludesachapteronWntsignalinginlymphopoiesis. Analysisof thisevolutionallyconservedpathwaywhichregulatescellularproliferation anddifferentiationindiversedevelopmentalcontextsbenefitedenormo- lyfromthediscoveryoftheLEF/TCFfamilyoffactorsinlymphocyticl- eages. ThisvolumeisdedicatedtothememoryofEugeniaSpanopoulou, ac- leagueandahighlyvaluedmemberofourscientificcommunity. Itc- tainsachapteronthebiochemistryofV(D)JrecombinationthatEugenia co-authoredwithDavidSchatz. Obituary Eugenia Spanopoulou was an extraordinary person and scientist. Her enormousintelligenceandenergysparkedimportantscientificdiscoveries, andvaultedhertoapointofbreathtakingpotential apotentialabruptly erasedattheageof37withthecrashofSwissairflight111onSeptember 3,1998. Lostwithherwereherhusband, AndrewHodtsev, andyoungson, Platon. Eugeniawaspassionatelyinterestedinunderstandingthemolecular- sisofdevelopmentandchoseashermodelsystemthedevelopmentofB andTlymphocytes. Shebeganbystudyingthetranscriptionalregulation oftheTcell-specificgene, Thy-1, asagraduatestudentinFrankGrosveld s labatMillHill, London. Thereafter, sheturnedherattentiontothetopicof V(D)Jrecombination, firstasapostdoctoralfellowwithDavidBaltimore attheWhiteheadInstituteinCambridge, Massachusettsandsubsequently inherownlaboratoryatMountSinaiSchoolofMedicineinNewYorkCity. Eugeniamadefundamentaldiscoveriesconcerningthebiochemicalme- anismofthisreaction, andhowdefectsinitscentralenzymaticcom- nents, RAG1andRAG2, canleadtoahumanseverecombinedimmuno- ficiencydisorder, knownasOmennsyndrome. Atthetimeof herdeath, shehadbeenaHowardHughesMedicalInstituteinvestigatorforlessthan ayear, buthadalreadyassembledalaboratoryof15peopleworkingonan extensivearrayoftopicsinearlylymphocytedevelopmentandV(D)J- combination. Eugenialivedeachmomentofherlifewithanintensityfittingforthe cityinwhichshelived. LikeManhattan, shesleptlittle. Sheexpectedagreat dealofherself, andonlyalittlelessfromthosewithwhomsheworked. - geniaalsohadhighexpectationsforthescientificprocessandwasouts- keninherpraiseorcondemnationofthosewhometorfellshortofthose expectations. Shewasquicktoformanopinionanddevotedherselffe- ciouslytofriendshipsandhypotheses. PerhapsthegreatesttestimonytoEugeniaistheaffectionandreverence feltforherby themembersof herlab. Whilethisstemmedinnosmall partfrompredictablesources herkeenmindandbroadknowledge it founditsdeepestsourceinEugenia sabilitytotransmit, byexampleand word, her love of a life of learning and exploration. SandroSantigata, a graduatestudentinEugenia slab, capturedthiseloquentlyatthememorial serviceforEugeniaandAndrew, whenhesaid: VIII Obituary Ifyouhaveeverbeenspellboundbyagreatstatue, enrapturedbyits strengthandvitality, enthralledbyitspurity, purposeandgraceandupli- edbythesenseofhopethatitsparkswithinyoursoul, thenyouhave- readyunderstoodwhyIadoredEugenia. Shesimplyembodiedtheideal- ticprinciplesthatformthecoreofadedicatedgraduatestudent sheart. Andtoseethesevaluesmaterializedintheformofone smentorcanbe nothingshortofinspirational. ListofContents GeneRegulatoryNetworksOrchestratingBCellFateSpecification, Commitment, andDifferentiation K. L. Medina.H. Singh. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Helix-Loop-HelixProteinsinLymphocyteLineageDetermination B. L. Kee. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Ikaros-FamilyProteins: InSearchofMolecularFunctions DuringLymphocyteDevelopment B. S. Cobb.S. T. Smale. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 BiochemistryofV(D)JRecombination y D. G. Schatz.E. Spanopoulou. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Thepre-BcellReceptorinBCellDevelopment: RecentAdvances, PersistentQuestionsandConservedMechanisms M. R. Clark.A. B. Cooper.L. D. Wang.I. Aifantis. . . . . . . . . . . . . . . . . 87 TranscriptionalControlofBCellActivation L. M. Corcoran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 ExpressionofMHCIIGenes G. Drozina.J. Kohoutek.N. Jabrane-Ferrat.B. M. Peterlin. . . . . . . . . 147 ClassSwitchRecombination: AnEmergingMechanism A. L. Kenter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 Blimp-1;ImmunoglobulinSecretion andtheSwitchtoPlasmaCells R. Sciammas.M. M. Davis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 WntSignalinginLymphopoiesis A. Timm.R. Grosschedl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 ListofContributors (Theiraddressescanbefoundatthebeginningoftheirrespectivechapters. ) Aifantis, I. 87 Kohoutek, J. 147 Clark, M. R. 87 Medina, K. L. 1 Cobb, B. S. 29 Peterlin, B. M. 147 Cooper, A. B. 87