Selection of similar naive T cell repertoires but induction of distinct T cell responses by native and modified antigen.
To study the T cell responses induced by native and modified Ag, we have followed in vivo TCR selection and cytokine profile of T cells, as well as the isotype of induced Abs, in response to the model Ag hen egg-white lysozyme (HEL) and its reduced and carboxymethylated form (RCM-HEL). RCM-HEL induces in vivo a T cell response focused on the same immunodominant determinant characterizing the response to native HEL, but further skewed to the Th1 pathway. No difference between HEL and RCM-HEL could be observed in the efficiency of processing, nor in the type of APCs involved. In vivo experiments show that coimmunization with HEL and RCM-HEL generates distinct Th2 or Th1 responses in naive mice, but the two forms of Ag expand the same HEL-specific public clonotype, characterized by the Vbeta8.2-Jbeta1.5 rearrangement, indicating that the populations of naive T cells activated by the two Ag forms overlap. T cells primed by RCM-HEL are restimulated by soluble HEL in vivo, but divert the phenotype of the HEL-specific response to Th1, implying that priming of naive T cells by a structurally modified Ag can induce Th1-type memory/effector T cells more efficiently than native Ag.
BioXell, Milano, Italy.
Francesco
F
Ria
Alexandra
A
Gallard
Claudia Raja
CR
Gabaglia
Jean-Charles
JC
Guéry
Eli E
EE
Sercarz
Luciano
L
Adorini
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D007114:Immunization; D016056:Immunodominant Epitopes / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007399:Interphase / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007132:Immunoglobulin Isotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta; C421864:hen egg lysozyme; D009113:Muramidase