A minimal level of MHC class II expression is sufficient to abrogate autoreactivity

The establishment of CD4(+) T cell tolerance requires that self-reactive th ymocytes are negatively selected during thymic development. A threshold of antigen concentration appears to exist for both MHC class I- and class II-m ediated negative selection, below which clonal deletion of a self-reactive transgenic TCR does not occur. Similarly, both the specificity and thymic c oncentration of MHC molecules affect the efficiency with which autoreactive thymocytes are deleted. However, this threshold for MHC class II concentra tion has not been well established. Here, we show that this threshold must be extraordinarily low. We have used the human lysozyme promoter to re-expr ess an A(beta)(b) cDNA on macrophages and other phagocytic myelomonocytic c ells of class Il-deficient A(beta)(b) -/- mice. Surface expression of I-Ab could be detected on mature peritoneal macrophages and, minimally, on thymi c dendritic cells; however, this level of expression was not sufficient for antigen-specific T cell activation. Nevertheless, when backcrossed onto an autoreactive K14 background, this minimal level of class II was sufficient to induce negative selection of a polyclonal self-reactive population. We conclude that provision of extremely low levels of class II to thymic dendr itic cells confers on them the ability to mediate clonal deletion of autore active T cells.