Medical Microbiology

basicproteininmultiplesclerosis,againstcollagendeterminantsinpoly-

arthritis,andagainstisletcellcomponentsindiabetes.

TransplantationImmunity.........................................

&Transplantrejectionwithinthesamespeciesislargelyaconsequenceof
MHC-restrictedT-cellrecognitionofforeignMHCantigens.Interspeciesre-
jectionisadditionallycontributedtobyantibodies,andintolerancebetween
complementactivationmechanisms.Methodsforreducing,orpreventing,
rejectionincludegeneralimmunosuppression,toleranceinductionbymeans
ofcellchimerism,andsequesteringofthetransplantedcellsororgan. &

ThestrongtransplantationantigensareencodedwithintheMHCcomplex(see

p.58ff.),whilsttheweakantigensconstitutetheMHC-presentedallelicdif-

ferencesofnonMHC-encodedhostproteinsorpeptides.Itispossibletodiffer-

entiatebetweenthehost-versus-graft (HVG)reactionoftherecipient

againstageneticallyforeigntissueororgan,andthegraft-versus-host

(GVH)reaction.

TheGVHreaction.Thistypeofreactionresultswhenimmunologicallyrespon-

sivedonorTcellsaretransferredtoanallogeneicrecipientwhoisunableto

rejectthem(e.g.,followingabonemarrowtransplantintoanimmuno-in-

competentorimmuno-suppressedrecipient).Thetargetsagainstwhich

thetransplantedTcellsgenerateanimmuneresponseincludetheMHCclass

IandIImoleculesoftherecipient.Therecipient’stransplantationantigens

alsopresentallelicvariantsofrecipientself-peptides,whichcanberecog-

nizedbydonorTcellsasweaktransplantationantigenswhenpresented

bycommonMHCalleles(itisconceivablethatstrongrecipienttransplanta-

tionantigenscouldbeacceptedandprocessedbydonorAPCs,howevereven

ifthisdidoccuritwouldbeoflimitedfunctionalconsequenceastheywould

notbepresentedbytherecipientAPCinthecorrectantigenconfiguration).

Weakhistocompatibilityantigens—forinstancethosepeptidevariantsrecog-

nizedasnonselfwhenpresentedincombinationwithessentiallyhistocom-

patibleMHCmolecules—playamoresignificantroleinbonemarrowtrans-

plants.Theexistence,andpathologicalrole,ofweaktransplantationantigens

hasonlybeendemonstratedincompletelyhistocompatiblesiblingsorwithin

inbredanimalstrainswithidenticalMHC.Thewidevarietyofalloreactive

Tcellscanbeexplainedbycross-reactivity,aswellasbytheenormousnum-

berofdifferentcombinationsofMHCmoleculesandcellularpeptides.Itmust

beemphasizedthatallogeneicMHCantigensonAPCsandlymphocytes(so-

calledpassengerlymphocytes)derivedfromthedonororganareparticularly

immunogenicsincetheyexpresshighlevelsofantigensandcantrafficto

TransplantationImmunity 115

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Kayser, Medical Microbiology © 2005 Thieme

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