I MMUNE SUPPRESSI ON IN VI VO W I TH ANTI GEN- MODI FI ED SYNGENEI C CELLS I . T-Cel l -Medi at ed Suppr essi on to t he Ter pol ymer pol y- ( Gl u, Lys, Phe) n * BY NAI - KONG CHEUNG, DAVI D H. SHERR, KRI KOR M . HEGHI NI AN, BARUJ BENACERRAF, AND MARTI N E. DORF Fr om t he Depart ment of Pat hol ogy, Har var d Medi cal School , Bost on, Massachuset t s 02116 I nt r avenous i nj ect i on of hapt en- conj ugat ed syngenei c cel l s r esul t s in speci f i c im- munol ogi cal t ol er ance af f ect i ng bot h hapt en- speci f i c cont act sensi t i vi t y and pl aque- f or m i ng cel l r esponses ( 1- 4) . Al t hough t he under l yi ng basi s f or t hi s nonr esponsi veness is not f ul l y under st ood, it appear s t hat bot h t he T- and B- cel l compart ment s may be af f ect ed ( 3- 5) . In addi t i on, sever al st udi es have r epor t ed t he gener at i on of speci f i c suppr essor T cel l s under t hese condi t i ons ( 4- 6) . The ant i gen t hat was used to i nduce speci f i c nonr esponsi veness ( suppr essi on) in t hese st udi es was t he synt het i c l i near pol ypept i de of L- gl ut am ic aci d, L- l ysi ne and L- phenyl al ani ne ( GLO) . 1 Thi s ant i gen was chosen f or sever al r easons . ( a) The i mmune r esponse to GL4 is under hi st ocompat i bi l i t y- l i nked i mmune r esponse gene cont r ol ( 7) . ( b) Al t hough pr evi ous at t empt s to i dent i f y GLO speci f i c suppr essor T cel l s in nonr e- sponder m i ce have been unsuccessf ul ( 8, 9) , we quest i oned whet her i nduct i on with ant i gen-modi f i ed syngenei c cel l s woul d be a mor e ef f i ci ent means of i nduci ng T suppr essor cel l s . (c) In addi t i on, we sought to pr ovi de evi dence t hat nonr esponder m i ce coul d gener at e f unct i onal T cel l s with speci f i ci t y f or GLO . To dat e, al l syst ems t hat anal yzed nonr esponsi veness i nduced with ant i gen-modi f i ed syngenei c cel l s empl oyed smal l , chem i cal l y r eact i ve mol ecul es whi ch wer e coval ent l y conj ugat ed to cel l sur f ace pr ot ei ns . In t he pr esent st udy, we have used a di f f er ent met hod of coupl i ng ant i gen to spl een cel l s . Thi s new coupl i ng met hod uses t he abi l i t y of pal m i t oyl - der i vat i zed pol ypept i des to adher e to cel l membr anes . Thus, pol ypept i des can be coupl ed ont o spl een cel l s wi t hout excessi ve chem i cal modi f i cat i on of t he pept i de and wi t hout t he f ormat i on of coval ent bonds bet ween t he pol ypept i de ant i gens and any cel l sur f ace mol ecul es . We now demonst rat e t hat t he i nt r avenous adm i ni st r at i on of syngenei c spl een cel l s modi f i ed with a pal m i t oyl - der i vat i zed pol y- pept i de r esul t s in ant i gen- speci f i c nonr esponsi veness and t he i nduct i on of speci f i c suppr essor T cel l s . * Suppor t ed by gr ant s AI - 13419 and AI - 00152 f r om t he Nat i onal I nst i t ut es of Heal t h, and by gr ant PCM75- 22422 f r omt he Nat i onal Sci ence Foundat i on . ' Abbr evi at i ons used in t hi s paper : C, compl ement ; GL, pol y- ( L- Gl uso- L- Lys" ) zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM ; GLO, pol y- ( L- GI u' - L- Lys' - L- Phe) ; Fy G, f owl gamma gl obul i n ; GLO- Fy G, coval ent conj ugat e of G14 and FyG ; GL- Fy G, coval ent conj ugat e of GL and FyG ; M/ P, suspensi on of Maal ox and per t ussi s vacci ne in PBS ; MEM, m i ni mal essent i al medi um; NMS, nor mal mous e ser um ; PBS, phosphat e- buf f er ed sal i ne ; PFC, pl aque- f or m i ng cel l s; SRBC, sheep er yt hr ocyt es ; p- GL¢, t he pal m i t oyl der i vat i ve of GLr b ; p- GL¢- spl cel l s, pGL¢- coupl ed spl een cel l s. J . Ex p. MED . © The Rockef el l er Uni ver si t y Pr ess - 0022- 1007/ 78/ 1201- 1539$1 . 00 1539 Vol ume 148 December 1978 1539- 1549