Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented.
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.
Escande-Beillard
Nathalie
N
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Washburn
Lorraine
L
Zekzer
Dan
D
Wu
Zhongqi-Phyllis
ZP
Eitan
Shoshy
S
Ivkovic
Sonja
S
Lu
Yuxin
Y
Dang
Hoa
H
Middleton
Blake
B
Bilousova
Tina V
TV
Yoshimura
Yoshitaka
Y
Evans
Christopher J
CJ
Joyce
Sebastian
S
Tian
Jide
J
Kaufman
Daniel L
DL
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
D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides