Evidence for CD8-independent T cell maturation in transgenic mice

Double-negative (CD4^-/CD8^-) T cells expressing the α/β transgenic TCR from the 2C cell line (anti-H-2L(d)) were examined in the periphery of animals whose MHC type produces positive, negative, or no selection for differentiation of the TCR on single positive (CD8⁺) cells. Regardless of the selection haplotype the CD4^-/CD8^- cells are capable of activation by anticlonotypic mAb indicating that negative selection does not inactivate the 'forbidden' TCR. Rather, the lack of response to H-2L(d) in the negative haplotype is likely the absence of CD8 required to produce a functional response to H-2L(d). The similarity of surface phenotype and functional activity of these CD4^-/CD8^- cells maturing in different haplotypes suggests they may arise by an alternative lineage which, unlike the dominant TCR α/β pathway, does not require coexpression of CD4/CD8.