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

Abstract

This report characterizes T-cell lines developed against peptide fragments of the neuroendocrine hormones, corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC). A MHC Class II binding moth containing a serine (S) and glutamic acid (E) residue separated by five intervening amino acids was used as a template for synthesizing peptides that may serve as T-cell epitopes. T-cell lines were generated specifically against a 17-amino-acid peptide of POMC or CRH peptide. These T-cell lines were predominantly CD4+ T cells and proliferated in an antigen-specific fashion. Further more, proliferation of T-cell lines specific for peptide-hormones could be inhibited by anti-MHC Class II antibody. In vitro the whole CRH protein could be processed and recognized as antigenic by CRH peptide-specific T cells. In addition, POMC-specific 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 specifically proliferate to self-proteins of the hypothalamic-hypophyseal 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 gland, or T-cell regulation, is the subject of ongoing investigation. © 1994 Academic Press. All rights reserved.