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

2009; American Association of Immunologists; Volume: 184; Issue: 2 Linguagem: Inglês

10.4049/jimmunol.0902159

1550-6606

Nathalie Escande‐Beillard, Lorraine Washburn, Dan Zekzer, Zhongqi-Phyllis Wu, Shoshy Eitan, Sanja Ivković, Yuxin Lu, Hoa Dang, Blake Middleton, Tina Bilousova, Yoshitaka Yoshimura, Christopher J. Evans, Sebastian Joyce, Jide Tian, Daniel L. Kaufman,

Immunotherapy and Immune Responses

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.