Over coming the crypticity of a viral T cell Determinant by insertion into a chimeric bacterial protein |
| |
Authors: | Lo-Man Richard; Martineaue Pierre; Manoury-Schwartz Benedicate; Hofnung Maurice; Leclerc Claude |
| |
Institution: | Unité de Biologie des Régulations Immunitaires, Institut Pasteur 25 rue du Docteur Roux Paris, France
1 Unite de Programmation Moleculaire et Toxicologie Génétique (CNRS UA 1444), Institit Pasteur Paris, France
2 Unité INSERM U283, Hospital Cochin Paris, France |
| |
Abstract: | Among the potential T cell determinants contained In a proteinantigen, the T cell response only focuses on a few immunodomlnantT cell determinants, whereas cryptic epitopes remain hiddento the Immune system. In the present work, we have studied theantigen processing and presentation of the C3: 93-115 sequenceof Mahoney pollovlrus VP1 protein, which Is Immunodomlnant InH-2d but cryptic In H-2s and H-2q mouse MHC haplotypes. Forthis purpose, we genetically Inserted the C3 determinant Intofive internal sttes of a bacterial protein, the maltose bindingprotein of Escherichla coll (MalE). In four out of five Insertionsites of MalE, the C3 determinant retained Its Immunodominancewhen the purified hybrid proteins were Injected to BALB/c (H-2d)mice. Moreover, In SJL/J (H-2d) mice, in three out of five MalE-C3constructs, the new structural environment of the cryptic C3epltope rescued Its processing and its in vivo presentationto T cells. In contrast, In DBA/1 (H-2d) mice, although MalE-C3chimeric proteins were correctly processed in vitro, the C3epitope remained cryptic in vivo. In this case, the impairmentto stimulate a T cell response in vivo was correlated with ashort time persistence of C3 peptides bound to Aq moleculesat the surface of live antigen-presenting cells. These resultsemphasize the role of flanking residues on the lack of processingof cryptic determinants and the Importance of the life spanof peptlde-MHC complexes to stimulate T cell responses. |
| |
Keywords: | CD4+ T cell chimeric protein immunodominance MaIE |
本文献已被 Oxford 等数据库收录! |
|