Selection of Similar Naive T Cell Repertoires but Induction of Distinct T Cell Responses by Native and Modified Antigen

• Published in: The Journal of immunology (1950) Vol. 172; no. 6; pp. 3447 - 3453
• Main Authors: Ria, Francesco, Gallard, Alexandra, Gabaglia, Claudia Raja, Guery, Jean-Charles, Sercarz, Eli E, Adorini, Luciano
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.03.2004
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antigen Presentation; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens - administration & dosage; Antigens - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Cell Differentiation - immunology; Clone Cells; Epitopes, T-Lymphocyte - biosynthesis; Epitopes, T-Lymphocyte - immunology; Female; Immunization; Immunodominant Epitopes - biosynthesis; Immunoglobulin Isotypes - biosynthesis; Interphase - immunology; Lymphocyte Activation - immunology; Methylation; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred CBA; Muramidase - administration & dosage; Muramidase - immunology; Muramidase - metabolism; Oxidation-Reduction; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.6.3447

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.