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 hypothalamoneurohypophysial (NHP) system. T
he central T-cell tolerance of the NHP neuroendocrine functions have b
een proposed to be mediated through these thymic NHP-related peptides
due to their close homology with the NHP neurohormones OT and vasopres
sin (VP). In order to investigate their putative presentation by prote
ins of the major histocompatibility complex (MHC), human thymic membra
nes were purified and passed through an immunoaffinity column using mA
b B9.12 directed to the monomorphic determinant of human MHC class I p
roteins. This methodology provided the following observations: (1) a N
P-like protein is translocated in human thymic membranes and is retain
ed 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 b
lots with mAb B9.12. The precise extent of this relationship between t
he thymic NP-like protein and the Ig/MHC superfamily is actually inves
tigated through the characterization of the genetic mechanisms respons
ible for the thymic expression of NHP-related peptides. Given the phys
iological importance of OT and of its binding to NP for transport alon
g the axonal processes of the NHP tract, we postulate that, somewhat a
nalogously, the thymic NP-/MHC class I-related protein could be involv
ed in the presentation of the OT-like peptide to immature T-cells.