Studies were carried out on the effects of a tetrapeptide tuftsin (Thr-Lys-Pro-Arg)1 associated with the Ig heavy chain, to increase the capacity of antigen pulsed macrophages to 'educate' T-lymphocytes. We demonstrated that a simultaneous application of KLH and synthetic tuftsin to monolayers of macrophages, increased significantly the lymphoproliferative response of lymph node cells recruited by initiator T-cells which were generated in culture on the macrophage monolayers. Tuftsin coupled covalently at its C-terminal site to BSA increased antibody response to BSA. We compared the effects of various synthetic structural analogues of tuftsin on the activation of the immunogenic effects of the antigen presenting macrophage. These experiments indicated that tuftsm activates the immunogenic macrophages not by stimulating phagocytosis, i. e., not by increasing the uptake of antigen by the macrophages. Its effect seems to be controlled by the stero-specific properties of the tetrapeptide determined by the specific sequence of the amino acids. It appears, however, that the dominant entity for the stimulation of the immunogenic macrophage is the Pro-Arg sequence. Since quite a number of peptide-hormones seem to possess Pro-Arg or Arg-Pro sequences, this may indicate a general principle for the activation of the programmed state of cells.
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