Expression of nonclassical MHC class I (RT1‐U) in certain neuronal populations of the central nervous system

Abstract

Major histocompatibility complex (MHC) class I genes consist of classical (Ia) and nonclassical (Ib) types. Recently, a set of structurally similar MHC class Ib genes in the rat, denoted RT1-U, was described. We here demonstrate expression of RT1-U mRNA using highly stringent oligonucleotide in situ hybridization in several different neuronal populations, including different motor nuclei and the substantia nigra in the rat MHC (c) and (n) haplotypes under normal conditions. The expression pattern for beta2-microglobulin mRNA was almost identical. In contrast, neuronal expression of classical MHC class I (RT1-A) was low. Interestingly, after mechanical nerve injury, glial cells predominantely upregulated expression of RT1-A, whereas neuronal expression of RT1-U remained unchanged. Neuronal expression of nonclassical MHC class I may thus be important for immune surveillance in the nervous system.

A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy

“…For example, an up-regulation of MHC class I expression is seen in motoneurons after axotomy (13,14) and hippocampal neurons in response to kainate-induced seizures (2), whereas there is a down-regulation in lateral geniculate nucleus neurons deprived of visual input (2). After axotomy of motoneurons, MHC class I is also up-regulated in microglia surrounding axotomized motoneurons (13,29,30), and may be induced in astrocytes both in vitro and in vivo (31). The fact that neurons seem to express ''nonclassical'' non-or oligomorphic MHC Ib molecules, whereas glial cells express ''classical'' polymorphic MHC Ia (30), may offer an opportunity to further characterize the recognition and signaling pathways in the response described here.…”

Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

“…We observed consistent increases in both classical (class Ia) and nonclassical (class Ib) MHC-I transcript expression in virus-infected samples (Table 6). Little is known about the role of nonclassical MHC presentation, but it has been suggested that expression on neurons might be protective (31,35). Transcription of other components of the MHC-I antigen presentation system were increased as well, including genes for the Tap transporters (Tap1 and Tap2) and (gamma interferon-inducible) activators of the immunoproteasome (PA subunits Psmb8, Psmb9, Psme1, and Psme2).…”

Beta-2-Microglobulin in Autism Spectrum Disorders

“…This was one of many factors believed to contribute to the "immuneprivileged" status of the brain. However, several studies have now shown that MHC I is in fact expressed by healthy neurons [21,22,36] . Furthermore, MHC I has several non-immunological roles and is involved in several aspects of neuronal development and function.…”