Ontogeny of T cells is accomplished in the thymus by a process of positive selection, in which interaction of the T cell receptor (TcR) expressed on CD4+8+ thymocytes with self major histocompatibility complex (MHC), expressed on cortical epithelial cells, determines the progress along the maturation pathway and confers self restriction to T cells. Conversely, cells behaving as self reactive by interaction with bone marrow-derived antigen-presenting cells are negatively selected by apoptosis. We show here that the presence of a class I-restricted soluble TcR (sTcR) in the fetal thymic microenvironment, early in T cell ontogeny, determines an enhanced negative selection of a sizeable number of CD4+8+ thymocytes, which have been previously subjected to a positive-selection event. We hypothesize that the generation of the mature thymic T cell repertoire stems from an interaction of TcR, under a critical affinity threshold, with a self peptide-MHC complex which is common to a great number of TcR specificities using the same restriction element. A shift in this affinity threshold, caused by sTcR, results in the generation of cells acting in a self-reactive manner, which are then deleted. In extended fetal thymus organ culture in the presence of sTcR, we have also observed the appearance of mature CD8+ T cells,which once adoptively transferred to syngeneic nude mice are expanded in the periphery, consistent with an enhanced avidity of these cells for self MHC.
Early degenerate selection of thymocytes by class I major histocompatibility complex / F Grassi, E Barbier, PA Cazenave. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 24:3(1994), pp. 627-634.
|Titolo:||Early degenerate selection of thymocytes by class I major histocompatibility complex|
GRASSI, FABIO MARIA (Primo)
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||1994|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/eji.1830240321|
|Appare nelle tipologie:||01 - Articolo su periodico|