The effect of thymus environment on T cell development and tolerance

During development in the thymus, T cells are deleted if their receptors are able to recognize self major histocompatibility complex (MHC) proteins. We show that such clonal deletion can occur because of interaction between receptors on T cells and MHC expressed on bone marrow-derived cells. In addition, development in the thymus picks out T cells to mature if their receptors will be restricted for antigen recognition in association with self MHC alleles expressed on thymus epithelial cells. This process is usually thought to involve positive selection of T cells bearing receptors with high and low affinity for MHC on thymus epithelium, and subsequent deletion of high affinity cells by interaction with bone marrow-derived cells. Our data do not fit such a model, but rather suggest that MHC molecules on thymus epithelium and bone marrow-derived cells may not be seen identically by T cell receptors.