T cells specific for hapten-modified self are precommitted for self major histocompatibility complex antigens before encounter with the hapten.

Abstract

The technique of antigen-driven, 5-bromo-deoxyuridine and light suicide was adapted to eliminate the precursors of cytotoxic effector cells for alloantigen and for 2,4,6-trinitrophenyl(TNP)-modified stimulator and target cells. Precursors of killer cells specific for alloantigen can be suicided independently of precursors of killer cells specific for TNP-modified self cells. The loss of activity during this procedure is not due to either specific or nonspecific suppressor cells, as judged by mixing experiments. Using responder cells from F1 animals showed that precursors specific for TNP-modified cells from 1 parent are suicided independently of precursors specific for TNP-modified cells of the other parent, but only if the parental strains differ in the K and D regions of the H-2 complex. Cells of F1 mice derived from K and D identical, I region different, parental strains were specifically suicided by TNP-modified stimulator cells from either parent. The cross-reactive killing of TNP-self targets induced by stimulation with allogeneic cells is not eliminated by first suiciding with TNP-parental cells, suggesting that the precursors of these 2 types of TNP-self killer cells are different. This is compatible with reported differences in their specificity. Deletion of alloreactive cells by this technique reveals little or no reactivity specific for TNP-modified allogeneic stimulator cells. Recognition of self MHC [major histocompatibility complex] antigens is probably preprogrammed in peripheral T [thymus derived] cells of normal animals, and is not acquired during the immunization process. Cells specific for modified alloantigen are relatively rare in the strains of mice studied.