title: Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented.
abstract: Studies of mice lacking MHC class I (MHC I)-associated proteins have demonstrated a role for MHC I in neurodevelopment. A central question arising from these observations is whether neuronal recognition of MHC I has specificity for the MHC I allele product and the peptide presented. Using a well-established embryonic retina explant system, we observed that picomolar levels of a recombinant self-MHC I molecule inhibited neurite outgrowth. We then assessed the neurobiological activity of a panel of recombinant soluble MHC Is, consisting of different MHC I heavy chains with a defined self- or nonself-peptide presented, on cultured embryonic retinas from mice with different MHC I haplotypes. We observed that self-MHC I allele products had greater inhibitory neuroactivity than nonself-MHC I molecules, regardless of the nature of the peptide presented, a pattern akin to MHC I recognition by some innate immune system receptors. However, self-MHC I molecules had no effect on retinas from MHC I-deficient mice. These observations suggest that neuronal recognition of MHC I may be coordinated with the inherited MHC I alleles, as occurs in the innate immune system. Consistent with this notion, we show that MHC I and MHC I receptors are coexpressed by precursor cells at the earliest stages of retina development, which could enable such coordination.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90024, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Escande-Beillard
authors.forename: Lorraine
authors.initials: L
authors.lastname: Washburn
authors.forename: Dan
authors.initials: D
authors.lastname: Zekzer
authors.forename: Zhongqi-Phyllis
authors.initials: ZP
authors.lastname: Wu
authors.forename: Shoshy
authors.initials: S
authors.lastname: Eitan
authors.forename: Sonja
authors.initials: S
authors.lastname: Ivkovic
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Lu
authors.forename: Hoa
authors.initials: H
authors.lastname: Dang
authors.forename: Blake
authors.initials: B
authors.lastname: Middleton
authors.forename: Tina V
authors.initials: TV
authors.lastname: Bilousova
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Evans
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Jide
authors.initials: J
authors.lastname: Tian
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kaufman
mesh_terms: D000483:Alleles; D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D053595:Embryonic Stem Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007113:Immunity, Innate; D051379:Mice; D016501:Neurites / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D012160:Retina / Q000196:embryology
chemical_list: D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides