Two features of HD are the loss of neurotransmitter receptors, especially glutamate receptors (GluR) and the tissue specific time dependant expansion of the CAG repeat of the mutant gene. I believe the mimicry of the shape changing CAG tract causes an immune response that leads to the devastation of HD. HD is in effect an auto-immune disorder with neurodegenerative consequences.

The following article tells us:

1. Self-specific antibodies are found in the brain.
2. The antibodies kill neurons.
3. The antibodies continue to kill neurons after the primary activating agent is removed.

The experimental evidence is that the cause and progression of HD are two different events. Understanding just how this happens will lead to effective treatments for HD. --Jerry 14Mar2001
J Clin Invest, March 2001, Volume 107, Number 5, 531

Autoantibodies to neuronal ion channels are implicated in several disorders of the central nervous system, including Rasmussen’s encephalitis, in which antibodies cross the blood-brain barrier and bind to glutamate-gated calcium channels (GluRs).

Binding of autoantibodies to GluR3 activates the channel and causes the death of specific populations of neurons. Although this condition can be modeled by immunizing animals with the GluR3 protein, it is not clear whether autoimmune responses to GluR3 normally initiate the disease. On the contrary, Koustova and coworkers now report that mice mount a specific immune response to the GluR proteins after being infected with the leukemia virus LP-BM5.

Self-specific antibodies accumulate in the neocortex and elsewhere in the brain, and Koustova et al. find that such brain-derived autoantibodies are biologically active, activating calcium channels in cultured cells and blocking interactions between these channels and their normal ligands.

These antibodies also kill cultured neurons, both by directing complement-mediated lysis and by excitotoxicity, in which elevated intracellular calcium concentrations lead to cell death. Because the antibody’s effects can be blocked by adsorbing away IgGs that bind to the virus itself, it appears that the self-reactivity of the antibody results from molecular mimicry between some viral epitope and the GluR proteins.

However, the authors note that preadsorbing the antibody with viral proteins only reduces and does not eliminate the effect of the antibodies on ligand binding to calcium channel, suggesting that epitope spreading after infection with the virus generates other channel-specific autoantibodies that can block channel function and promote neurodegeneration.