T cell recognition of cell-surface antigens. II. Antigen recognition is necessary yet not sufficient for triggering T cell-mediated immunity

We investigated whether recognition per se of cell surface antigens by lymphocytes is both necessary and sufficient to trigger sensitization of T cells. We assayed sensitization of normal rat lymphocytes against monolayers of mouse fibroblasts by measuring the acquisition of cytotoxicity against target monolayers syngeneic to the sensitizing monolayer, following 5 days of culturing on living or glutaraldehyde-fixed fibroblasts. Monolayers of either living or glutaraldehyde-treated fibroblasts were used as cellular immunoadsorbents to assay recognition. Glutaraldehyde treatment of mouse fibroblasts did not seem to alter the cell surface antigens detectable by alloantibodies. Yet, rat lymphocytes cultured on such monolayers did not undergo sensitization. This was not due to the lack of feeder effect by the glutaraldehyde-fixed monolayers, since the addition of living rat fibroblasts, which sustained the survival of the lymphocytes, did not result in sensitization. Not even when living fibroblasts were added to syngeneic fixed monolayers did sensitization of the rat lymphocytes against the monolayer cells occur. Yet, addition of living fibroblasts to fixed allogeneic monolayers resulted in sensitization against the living fibroblasts, but not against the fixed cells. To test whether lymphocytes recognize surface antigens of glutaraldehyde-treated monolayers, the capacity of the latter to specifically adsorb lymphocytes possessing receptors for the fibroblast antigen was measured. The nonadhering rat lymphocytes, seeded on glutaraldehyde-treated C3H fibroblasts, lost their capacity to become sensitized against fresh C3H cells, but retained their capacity to react against BALB/c fibroblasts. Recognition of C3H antigen did take place, yet this was not sufficient to trigger sensitization. Thus, rat lymphocytes seem to recognize the antigens of fixed monolayers, but cannot respond to them.