Open AccessTurning (Ir gene) low responders into high responders by antibody manipulation of the developing immune system.
Author(s) -
C Martinz,
Miguel A. R. Marcos,
Pablo Pereira,
Carlos Márquez,
Marisa Toribio,
Alberto De La Hera,
PierreAndré Cazenave,
Antönio Coutinho
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.11.3812
Subject(s) - idiotopes , biology , idiotype , congenic , immunology , major histocompatibility complex , antibody , immune system , antigen , epitope , hapten , microbiology and biotechnology , cd40 , monoclonal antibody , gene , genetics , cytotoxic t cell , in vitro
The ability of helper T cells directed against trinitrophenyl-modified syngeneic spleen cells to recognize low-hapten densities on target cells is under major histocompatibility complex-linked Ir gene control. Thus, BALB/c (H-2d) mice are low responders while H-2 congenic BALB.C3H (H-2k) mice are high responders. Immunization of adult BALB/c mice with the monoclonal antibody F6(51), directed to shared idiotopes by anti-trinitrophenyl antibodies and clonal receptors on anti-trinitrophenyl-self helper T cells, leads to the production of high titers of circulating idiotype, has no influence on helper T cell idiotypic profiles, but shifts to a high-responder phenotype the ability of helper T cells to recognize low-hapten densities. These effects on Ir gene phenotype are even more striking in untreated progenies from F6(51)-immunized BALB/c females, which are better responders than genetically high-responder BALB.C3H mice, although completely different in the expression of the F6(51)-defined clonotype. The general significance of these findings on Ir gene-directed T-cell repertoire selection is discussed, for they constitute formal evidence against antigen-presentation as a mechanism of Ir gene effects and strong support for the importance of maternal influences on the development of T-cell repertoires.