The specificity of heterozygous T cells for H-2-associated antigen in vivo was studied by inducing negative selection to sheep erythrocytes (SRC) in irradiated mice. Purified (CBA × C57BL/6)F1 T cells plus SRC were transferred to irradiated F1 or parental strain mice and then recovered from thoracic duct lymph 1 to 2 days later to measure T helper function. When F1 T cells were filtered with SRC through irradiated F1 mice the cells lost the capacity to stimulate anti-SRC responses by CBA, C57BL/6 or F1 B cells. The unresponsiveness was specific (normal responses were found against horse erythrocytes) and there was no evidence that suppression was involved. By contrast, F1 T cells filtered with SRC through irradiated mice of one parental strain failed to stimulate anti-SRC responses by B cells of this strain but retained the capacity to stimulate B cells of the opposite parental strain and F1 B cells. Both primed and unprimed T cells gave similar results and subsequent positive selection of the T cells to SRC in irradiated F1 mice for 5 days did not abrogate the restriction. The phenomenon was shown to be linked to the H-2 complex but not to Ig allotype.

The data provide further support for the view that F1 T cells comprise two subgroups of cells and imply that only one subgroup undergoes negative selection (is transiently withdrawn from the circulation) when exposed to antigen in irradiated mice of one parental strain. Both T cell subgroups undergo selection in irradiated F1 mice.

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