International Immunology, Vol. 11, No. 8, 1295-1306,
August 1999
© 1999 Japanese Society for Immunology
A minimal level of MHC class II expression is sufficient to abrogate autoreactivity
1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, and
2 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
3 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Correspondence to: T. M. Laufer, Division of Rheumatology, University of Pennsylvania, BRB2, Rm 753, 421 Curie Boulevard, Philadelphia, PA 19104, USA
The establishment of CD4+ T cell tolerance requires that self-reactive thymocytes are negatively selected during thymic development. A threshold of antigen concentration appears to exist for both MHC class I- and class II-mediated negative selection, below which clonal deletion of a self-reactive transgenic TCR does not occur. Similarly, both the specificity and thymic concentration of MHC molecules affect the efficiency with which autoreactive thymocytes are deleted. However, this threshold for MHC class II concentration has not been well established. Here, we show that this threshold must be extraordinarily low. We have used the human lysozyme promoter to re-express an Aßb cDNA on macrophages and other phagocytic myelomonocytic cells of class II-deficient Aßb –/– mice. Surface expression of I-Ab could be detected on mature peritoneal macrophages and, minimally, on thymic 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 dendritic cells confers on them the ability to mediate clonal deletion of autoreactive T cells.
Keywords: dendritic cell, lysozyme promoter, macrophage, MHC class II, negative selection
Transmitting editor: A. Singer
4 Present address: Department of Pediatric Oncology, University Hospital Groningen, 9700 RB Groningen, The Netherlands
5 Present address: Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USA
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