In vitro stimulation of spleen cells from mice immune to Sendai virus results in the generation of effector cells that lyse unmodified allogeneic target cells in addition to syngeneic cells modified by virus. These cells are immunologically specific because their lysis may be blocked by cold targets syngeneic to either the stimulator or the responder. These results support our proposal that the development of alloreactivity can be explained by the crossreactivity between modified self major histocompatibility complex antigens and alloantigens. We propose that exposure to autologous major histocompatibility complex antigens modified by foreign antigens in our environment results in the expansion of the pool of T cells that will respond to alloantigens sharing crossreactive determinants.
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