Lymphocyte activation by oxidative modification: avidin-modified T cells activate biotin-modified autologous T cells...

Immunocompetent human thymocytes were oxidized by periodate and conjugated with either biocytin-hydrazide or avidin-hydrazide followed by reduction with borohydride. Without further treatment, the resultant modified cells alone exhibited moderate levels of activation as a function of exogenously added interleukin 2. However, strong interleukin 2-dependent stimulation was observed when avidin-modified cells and biotin-modified cells were mixed. The effect was inhibited by free biotin molecules. By selective inhibition procedures, it was found that the avidin-modified cells induced the stimulation of biotin-modified cells, but not vice versa. It is postulated that the polyvalent avidin-hydrazide molecule covalently crosslinks and "freezes" the movement of oxidized glycoconjugates on the membrane surface. In contrast, the monovalent biocytin hydrazide would enable the modulation of membrane components upon interaction with avidin. The results suggest that crosslinking of mobile sites at the T-cell surface are essential for the transmission of an oxidation-induced mitogenic signal.