Neurons Preferentially Respond to Self-MHC Class I Allele Products Regardless of Peptide Presented

• Published in: The Journal of immunology (1950) Vol. 184; no. 2; pp. 816 - 823
• Main Authors: Escande-Beillard, Nathalie, Washburn, Lorraine, Zekzer, Dan, Wu, Zhongqi-Phyllis, Eitan, Shoshy, Ivkovic, Sonja, Lu, Yuxin, Dang, Hoa, Middleton, Blake, Bilousova, Tina V, Yoshimura, Yoshitaka, Evans, Christopher J, Joyce, Sebastian, Tian, Jide, Kaufman, Daniel L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.2010
• Subjects: Alleles; Animals; Antigen Presentation; Autoantigens - immunology; Embryonic Stem Cells; Histocompatibility Antigens Class I - genetics; Immunity, Innate; Mice; Neurites - immunology; Neurons - cytology; Neurons - immunology; Peptides - immunology; Retina - embryology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902159

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.