Self la-recognizing T cells undergo an ordered series of interactions with ia-bearing substrate cells of defined function during their development: A model

  • Charles A. Janeway
  • Michael E. Katz
Hypothesis and Theory


A four-step scheme of cell interactions between self la-recognizing T cells in the helper T cell lineage and la-bearing substrate cells is proposed. The first interaction, with a veto cell, clears the repertoire of helper T cells specific for self Ia, or self antigens in association with self Ia. The second interaction, between helper T cells and Ia on thymic epithelium expands self Ia-recognizing T cells; T cell diotopes displayed on the epithelial cell surface may play the role of an internal antigenic image for this expansion. The third interaction occurs between antigen-presenting cell Ia plus nominal antigen and virgin Lyl T cells, leading to T cell activation and expansion. The fourth interaction involves B cells binding specific antigen via their Ig receptor and displaying self Ia, and this antigen-Ia complex is recognized by helper T cells, causing B cell proliferation and differentiation to antibody secretion. A regulatory pathway, involving suppressor T cells that recognize activated helper T cells via self Ia bound to the anti-self Ia receptor on the T cell surface, is also proposed. This model permits any or all of the proposed mechanisms of Ir gene ac tion, and is compatible with one or two site models of T cell receptors. Its main predictions are that Ia density is carefully regulated in substrate cells to allow both self tolerance and self recognition, in an ordered scheme of development.


Nominal Antigen Howard Hughes Medical Institute Thymic Epithelium Splenic Dendritic Cell Picryl Chloride 
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Copyright information

© S. Karger AG, Basel 1984

Authors and Affiliations

  • Charles A. Janeway
    • 1
  • Michael E. Katz
    • 1
  1. 1.Howard Hughes Medical Institute at Yale, Department of PathologyYale Medical SchoolNew HavenUSA

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