T-cell Clonal Anergy

  1. R.H. Schwartz,
  2. D.L. Mueller,
  3. M.K. Jenkins, and
  4. H. Quill
  1. Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

This extract was created in the absence of an abstract.

Excerpt

Two-signal Model for the Induction of a T-cell Proliferative Response

Chemical fixation of splenic antigen-presenting cells (APC) with paraformaldehyde or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI) destroys their ability to stimulate a proliferative response from interleukin-2 (IL-2)-producing T-cell clones (Jenkins and Schwartz 1987). In addition, exposure of the clones to antigen in the presence of the chemically fixed APC induces in them a hyporesponsive state to subsequent stimulation by normal APC and antigen (Fig. 1A). This induction of proliferative nonresponsiveness requires the correct allelic form of the major histocompatibility complex (MHC) class II molecule and the precise peptide recognized by the antigen receptor of the T-cell clone. These observations suggest that antigen-receptor occupancy is qualitatively normal and that the delivery of some other signal required for T-cell activation has been damaged by the fixation.

This concept is strengthened by experiments in which T-cell clones fail to proliferate in response to peptide presented by planar...

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