Planting and pruning in the brain: MHC antigens involved in synaptic plasticity?
- Max Planck Institute for Neurobiology, Am Klopferspitz 18a, 82152 Martinsried, Germany
MHC antigens count among the classical “immune” molecules. They act as platforms presenting antigenic peptides to the specific receptors on T cells. MHC class I molecules interact with the CD8+ “killer” T cell lineage, whereas class II molecules present antigen to CD4 “helper” T cells. In addition, some MHC proteins can be recognized by natural killer (NK) cells, where, depending on the nature and context of a particular receptor, they trigger either activating or suppressive signals. Additional roles such as in embryonic development or tissue organization have been postulated, but so far these hypotheses have not stood the test of molecular immunology (1). Now, this trend seems to be changing. In a recent issue of PNAS, Oliveira et al. (2) reported that MHC class I or Ib antigens are required to regulate synaptic pruning on neuronal bodies that undergo retrograde degeneration after axonal transection.
A role of MHC determinants in neural tissue response is surprising because, according to an imperial dogma, MHC determinants are missing in the CNS. The lack of MHC is one major factor interfering with immune reactivity in the healthy CNS, securing the brain's “immune privilege.” However, this is not the entire story, because MHC products, along with many other “immune” genes, are readily inducible in the CNS tissues under various pathological conditions, including autoimmune inflammation, microbial infection, and neuronal degeneration. The surprising relationship between brain degeneration and immune reactivity has been strikingly demonstrated …
