The involvement of major histocompatibility class I molecules in the synaptic plasticity, glial reactivity and axonal regeneration

Abstract

The class I major histocompatibility complex (MHC-I), which is present in all nucleated cells, is mostly known to present endogenous antigens to cytotoxic T lymphocytes (CTLs) from the immune system. In the central nervous system (CNS), the participation of the MHC-I in the synaptic plasticity process has been suggested. MHC-I is overexpressed on the neurites of damaged neurons and acts in the maintenance of inhibitory synapses, ensuring the energy stores to be directed towards the mechanisms of cell repair rather than an inefficient communication. Among the MHC-I ligands, the paired immunoglobulin-like receptor B seems to be a key molecule for the communication between neurons via MHC-I, since it unleashes inhibitory signals and may be found on neuronal branches. Not only neurons, but also other cells may be involved in the process of synaptic plasticity. In this way, microglias were shown to engulf injured neurons and favor synaptic striping, while CTLs were demonstrated to cut neurites that were presenting high levels of viral peptides by the MHC-I molecules. Based on the above, this project aims at evaluating the involvement of MHC-I and its ligands in the communication between neurons, as well as in the interaction between neurons and CTLs or microglias. We believe that he data herein obtained will contribute to a better comprehension of the mechanisms involved in synaptic plasticity process, as well as in the treatment of CNS degenerative diseases, in special, the auto-immune ones.