A novel T-lymphocyte molecule that may function in the induction of self-tolerance and MHC-restriction within the human thymic microenvironment

Abstract

T-cell differentiation is known to take place in the thymus, but the precise mechanisms involved remain unresolved. In order to analyse the role of the thymic microenvironment in thymocyte maturation and generation of the T-cell repertoire, we have raised monoclonal antibodies (mAb) to thymic stromal cells, and with these can recognize, in the non-lymphoid component of the thymus, several antigenically distinct compartments. One mAb, MR6, binds to both the cortical epithelium and medullary macrophages/dendritic (M phi/DC) cells in sections of the human thymus. Recently, the molecule detected by MR6 has also been detected at low levels on the surface of T lymphocytes. We now report that this molecule has a relative molecular mass of 145,000 (p145-MR6) and that this appears to be the same for both thymic lymphocytes and stromal cells. Functional studies show that mAb MR6 inhibits both the antigen-specific and the IL-2-induced proliferative response of MHC class II-restricted cloned helper T cells and peripheral blood mononuclear cells (PBMC). These results suggest that the molecule to which mAb MR6 binds could be responsible for the inhibition of T-cell proliferation to self-antigens, and hence may be involved in tolerance induction and MHC restriction.