THE T-CELL REPERTOIRE CONTAINS CELLS REACTIVE WITH HORMONES OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS - RECOGNITION OF SYNTHETIC PEPTIDE-FRAGMENTS OF CORTICOTROPIN-RELEASING HORMONE (CRH) AND PROOPIOMELANOCORTIN (POMC) IN THE LEWIS RAT

This report characterizes T-cell lines developed against peptide fragm ents of the neuroendocrine hormones, corticotropin-releasing hormone ( CRH) and pro-opiomelanocortin (POMC). A MHC Class II binding moth cont aining a serine (S) and glutamic acid (E) residue separated by five in tervening amino acids was used as a template for synthesizing peptides that may serve as T-cell epitopes. T-cell lines were generated specif ically against a 17-amino-acid peptide of POMC or CRH peptide. These T -cell lines were predominantly CD4(+) T cells and proliferated in an a ntigen-specific fashion. Further more, proliferation of T-cell lines s pecific for peptide-hormones could be inhibited by anti-MHC Class II a ntibody. In vitro the whole CRH protein could be processed and recogni zed as antigenic by CRH peptide-specific T cells. In addition, POMC-sp ecific T cells can recognize POMC peptide presented on the membrane of MHC Class II+ POMC T cells. These results indicate that the normal T- cell repertoire of the rat contains elements which can recognize and s pecifically proliferate to self-proteins of the hypothalamic-hypophyse al axis. Moreover, it seems that T lymphocytes themselves may present antigens which they synthesize. The relationship of these observations to autoimmune reactions affecting the hypothalamus and/or pituitary g land, or T-cell regulation, is the subject of ongoing investigation. ( C) 1994 Academic Press, Inc.