Recognition of idiotypic structures in the thymus.
During the passage through the thymus, T cells are selected which recognize self major histocompatibility complex (MHC) antigens with low avidity. Whether the T-cell repertoire for recognition of altered self is also built up intrathymically or in the periphery, and whether it is determined exclusively by external antigens or is shaped by the internal environment is still a matter of debate. This question was addressed by analysing the responsiveness of thymocytes during post-natal development towards a nominal antigen [trinitrophenyl (TNP)] and an anti-TNP monoclonal antibody (Sp6), which carries a recurrent idiotype. During the first weeks of life, in vitro cultures of thymocytes proliferated strongly in the absence of nominal antigen. Proliferation rates were not increased by the addition of nominal antigen [TNP-ovalbumin (OA)], but a significant increase was noted in the presence of Sp6, thymocytes recognizing the processed immunoglobulin. After in vivo stimulation with TNP conjugates, 'antigen-specific' clones could also be detected in the thymus, the frequency of clones proliferating in response to Sp6 being further augmented. With increasing age, the proliferative capacity of thymocytes from unstimulated and antigenically stimulated mice decreased significantly. Responsiveness of spleen cells (SC) differed in some respects. The response towards Sp6 decreased with age, while antigen-specific clones were detected at increasing frequencies during post-natal development. Furthermore, after antigenic stimulation, the frequency solely of antigen-specific, but not of Sp6-specific clones was increased. Thus, it appears that the T-cell repertoire is shaped already during the intrathymic passage, being influenced primarily by the B-cell repertoire and modulated further by external antigen.
Zöller
M
M
Institute for Radiology and Pathophysiology, German Cancer Research Center, Heidelberg.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000502:physiology; D001789:Blood Group Antigens; D000939:Epitopes / Q000276:immunology; D006736:Horses; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000032:analysis*; D013950:Thymus Gland / Q000032:analysis*; D014301:Trinitrobenzenes / Q000008:administration & dosage / Q000276:immunology
D000911:Antibodies, Monoclonal; D001789:Blood Group Antigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D008070:Lipopolysaccharides; D014301:Trinitrobenzenes; D010047:Ovalbumin