Membrane translocation and relationship with MHC class I of a human thymic neurophysin-like protein.
Thymic epithelial and nurse cells (TEC/TNC) synthesize an oxytocin (OT)-like peptide in association with a neurophysin (NP)-related protein in a way similar to in the hypothalamo-neurohypophysial (NHP) system. The central T-cell tolerance of the NHP neuroendocrine functions have been proposed to be mediated through these thymic NHP-related peptides due to their close homology with the NHP neurohormones OT and vasopressin (VP). In order to investigate their putative presentation by proteins of the major histocompatibility complex (MHC), human thymic membranes were purified and passed through an immunoaffinity column using mAb B9.12 directed to the monomorphic determinant of human MHC class I proteins. This methodology provided the following observations: (1) a NP-like protein is translocated in human thymic membranes and is retained by B9.12 on the column; (2) the MW of this NP-like material (50-55 kD) is quite different from the MW of hypothalamic NP proteins (10 kD), and (3) this thymic NP-like protein could be identified on Western blots with mAb B9.12. The precise extent of this relationship between the thymic NP-like protein and the Ig/MHC superfamily is actually investigated through the characterization of the genetic mechanisms responsible for the thymic expression of NHP-related peptides. Given the physiological importance of OT and of its binding to NP for transport along the axonal processes of the NHP tract, we postulate that, somewhat analogously, the thymic NP-/MHC class I-related protein could be involved in the presentation of the OT-like peptide to immature T-cells.
Geenen
V
V
Department of Endocrinology, University of Liège, Liège-Sart Tilman, Belgium.
Vandersmissen
E
E
Cormann-Goffin
N
N
Martens
H
H
Legros
J J
JJ
Degiovanni
G
G
Benhida
A
A
Martial
J
J
Franchimont
P
P
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D002675:Child, Preschool; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009481:Neurophysins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D017634:Self Tolerance; D013950:Thymus Gland / Q000378:metabolism*; D013951:Thymus Hormones / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D009481:Neurophysins; D013951:Thymus Hormones