This preview shows pages 1–2. Sign up to view the full content.
This preview has intentionally blurred sections. Sign up to view the full version.View Full Document
Unformatted text preview: demonstratedthattheconcentrationofan- tigen required fortoleranceofdouble posi- tive thymocytes isbelowthe concentration required to detectamatureTcell response (20). Ithasalsobeenshownthat presenta- tionof particularantigens inthe thymus candeleteadefined population of thymo- cytes, whereasthesame antigenspresented tomatureTcells expressing thesameTCR do not elicita response(21).Although someofthedifferences may beattributedto the comparison ofimmatureandmatureT cells, these experiments also suggest that the "avidity"required forT cellactivation is stronger than negative selection. Collectively, thesemodels suggest that differencesinthe affinity betweentheTCR andits ligand existfor positive selection, negative selection, andT cellactivation. One way to explain thedifferent develop- mental fatesoftheT cellhas been to invokethe presence oftwosetsof peptides, onefor low-affinity andonefor high-affinity interactions, thatmediate positive or neg- ative selection, respectively (22). Ourmod- elhasshownthatno special peptides are involvedin discriminating between positive or negative selection, sincetheviral pep- tide antigen thatis recognizedby matureT cellswillmediateboth positive and nega- tiveselection. Further experiments with unrelated H-2Dbbinding peptides will de- finehow precise theinteractionmustbefor positive selection.Our findingssuggest that the avidity oftheinteractionsbetweenthe thymocyte andstromalelementsisreflected by thenumberofTCRs engaged withMHC moleculesata given time.Thisinturn may alterthe strength ofintracellular signals. It is likely thatothermoleculesinfluencethe stability ofthe TCR:peptide-MHC interac- tionsand directly affectthe signalsgenerat- ed through theTCR.Furtherstudieswith thismodelwill help definethe key mole- culesandinteractions required forselection inthe thymus. REFERENCESAND NOTES 1.M.M. Davis,Annu.Rev.Biochem.59, 475 (1990). 2.R.M. Zinkernagel et al.,J. Exp. Med. 147,882 (1978); P.J.FinkandM.J.Bevan,ibid.148,766 (1978); L.J. Berg et al., Cell58, 1035 (1989); D. Cosgrove etal.,ibid.66,1051 (1991). 3.M. Zijlstra et al., Nature344,742 (1990);B.H. Koller,P.Marrack,J. W. Kappler,O.Smithies, Science248,1227 (1990). 4. F.RamsdellandB.J.Fowlkes,J.Immunol. 143, 1467 (1989); J.C. Zuniga-Pflucker etal., J. Exp. Med.169,2085 (1989); W. P. Fung-Leung etal., Eur.J.Immunol.23,212 (1993); A.Rahemtullaet al., Nature353,180 (1991); C.J.Aldrich et al., ibid. 352,718 (1991); N.Kileen,A. Moriarty, H.S. Teh, J. Exp. Med.176,89 (1992). 5.H.S.Tehetal.,Nature335,229 (1988); W.C.Sha etal.,ibid., p.271; J. Kaye etal.,ibid.341, 746 (1989). 6. LJ. Berg, G.D.Frank,M.M.Davis,Cell 60, 1043 (1990). 7. K.A. Hogquist, M.A.Gavin,M.J.Bevan,J. Exp. Med.177,1469 (1993)....
View Full Document
This note was uploaded on 01/07/2011 for the course BIPN BIPN 144 taught by Professor Bier during the Spring '10 term at UCSD.
- Spring '10