Cellular and molecular aspects of thymic T-cell education to neurohypophysial peptides

Our studies have shown that oxytocin (OT) is the dominant peptide of the neurohypophysial (NHP) family that is expressed by thymic epithelial/nurse cells (TEC/TNC). Both in specific RIA and ICC analyses, vasopressin (VP) immunoreactivity is considerably lower in TEC. OT is not secreted by TEC/TNC, but it is presented as the self antigen of the NHP family to developing pre-T cells. The process of T-cell education in recognizing the NHP family involves an active cooperation between this neuroendocrine gene/protein family and the immunoglobulin family. This cooperation is illustrated by the identification in plasma membranes of human TEC of a 55-kDa protein bearing a neurophysin (10 kDa), as well as a MHC class I heavy chain-related domain (45 kDa). Since both OT and VP genes are transcribed in the thymus, the site of this cooperation should be located at posttranscriptional level. From these data, it appears that thymic T-cell education to the NHP family involves specific pathways which are not strictly superimposible to those dlineated using peripheral dedicated APC. Although MHC class I pathways are needed, it appears that thymic T-cell education to NHP self is not restricted in an allelic fashion. This offers significant advantages for the selection of the human T-cell repertoire. Furthermore, the absence of a tight MHC allelic restriction in the process of T-cell education to neuroendocrine self opens novel perpectives for the prevention of autoimmune endocrine disorders such as insulin-dependent diabetes mellitus.