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 pro-opiomelanocortin (POMC) in the Lewis rat.
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 motif 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. Furthermore, 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.
Griffin
A C
AC
Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Zhao
W
W
Wegmann
K W
KW
Hickey
W F
WF
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000276:immunology* / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000737:chemistry*; D007376:Interleukin-2 / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000737:chemistry*; D011333:Pro-Opiomelanocortin / Q000276:immunology* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D007376:Interleukin-2; D010455:Peptides; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone