The Induction of Antigen Specific Unresponsiveness in Cloned T Lymphoctyes

Abstract

The recognition that T lymphocytes can be maintained in long term culture has allowed the isolation of monoclonal populations of antigen specific T lymphocytes. Such reagents have facilitated the analysis of the T cell repertoire, the genetic restriction of lymphoid cell inter-actions and receptor structure^1,2. Additionally, T cell clones have been useful for the analysis of mechanisms regulating the activation³ and induction of unresponsiveness⁴ in T cells. In the regulation of T cell unresponsiveness, antigen is also of importance since administered in vivo in either supraoptimal or repeated suboptimal concentrations antigen induces specific unresponsiveness termed immunological tolerance^5,6. In contrast to B cell tolerance^7,8 the in vitro investigation of the cellular mechanism of T cell tolerance generally has been lacking. Recently, however, we have isolated T lymphocyte clones reactive with a defined peptide (p20) located at the carboxyl terminus (306–329) of the HA–1 molecule of influenza haemagglutinin (HA)⁹ that can be rendered unresponsive by supraimmunogenic concentrations of that peptide in the absence of other lymphoid cells⁴. The present report reviews the antigen specificity, requirement for MHC recognition, phenotypic and biochemical changes occurring during antigen induced T cell unresponsiveness.