Clonal deletion of thymocytes expressing potentially self-reactive T cell receptors (TCRs) occurs during thymocyte ontogeny. Mice deficient for CD4 expression provide a unique model system to study the contribution of the CD4 molecule in negative selection of T cells reactive against the major histocompatibility complex class II-associated retroviral self-superantigen, Mls-1a. In the presence of Mls-1a determinants, mature CD8+ T cells expressing V beta 6, 8.1, and 9 were deleted in CD4-deficient mice, thus demonstrating that TCR affinity for Mls-1a is sufficient for deletion and that a signal through CD4 was not required. However, in instances where the TCR affinity for Mls-1a is low, as in the case of V beta 7+ T cells, CD4 expression was required for clonal deletion. These results demonstrate that for Mls-1a-mediated clonal deletion of T cells, the requirement for the accessory or coreceptor function of CD4 depends on the affinity of the TCR.
CD4 expression is differentially required for deletion of MLS-1a-reactive T cells.
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V A Wallace, A Rahemtulla, E Timms, J Penninger, T W Mak; CD4 expression is differentially required for deletion of MLS-1a-reactive T cells.. J Exp Med 1 November 1992; 176 (5): 1459–1463. doi: https://doi.org/10.1084/jem.176.5.1459
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