Boulanger and Shatz
Nat Rev. Neurosci, Vol 5, July 2004
Key concepts:
* neurons normally express MHC class I molecules in vivo
* MHCI molecules are important for our ability to identify foreigners from self
* recent results: uninjured neurons express both classical and nonclassical MHCI class genes in vivo
* role of neural activity: regulates MHCI experiments
* not quite consistent everywhere, one experiment showed that TTX led to upregulation of MHCI, and another experiment of TTX led to downregulation of MHCI. But those were in different systems, etc.
* need to characterize specific expression profile of MHCI in neurons and in developmental timepts
* need to clarify location, identity, and timing of MHC class I protein expression that is relevant to functional and structural events in neurons
* MHCI receptors that are expressed endogenously in the CNS - PirB is one of them
* there is evidence for a neuronal role of CD3-zeta
* in the immune system: functional TCR-beta transcripts are encoded by loci that have undergone somatic recombination
* but in the brain: the transcripts are products of direct splicing of loci that have not been rearranged
* MHCI-like molecule: FcRn involved in transport of maternal Ig across fetal intestinal epithelium
* long list of disorders implicating MHCI molecules
* obviously, there are crucial functions of MHCI proteins beyond the immune system
* one hypothesis: affected neurons must express both target antigen and appropriate MHCI molecule to present it
* PND: paraneoplastic neurological degenerative disorders. Primarily affect sites of high MHCI expression
* cellular immune response, e.g. tnf-a and so on, also have critical functions beyond the immune system.
* need to develop objective molecular or biochemical diagnostic criteria
* schizophrenia: a neurodevelopmental disorder, perhaps result of aberrant synaptic organization or loss of connections
* neuronal and immune system MHCI functions may share similar mechanisms.
