The spatio-temporal expression of MHC class I molecules during human hippocampal formation development

Zhang, Aifeng; Yu, Hong; He, Yao; Shen, Yuqing; Pan, Ning; Liu, Jiane; Fu, Bo; Miao, Fengqin; Zhang, Jianqiong

doi:10.1016/j.brainres.2013.07.001

Cited by 26 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Slides were stained with the monoclonal antibody HC-10, which recognizes b2m-free HLA-A3, -A10, -A28, -A29, -A30, -A31, -A32, -A33, and -B (excluding HLA-B5702, -5804, and -B73), the monoclonal antibody HCA-2 specific for b2m-free HLA-A (except HLA-A24), -B7301, and -G heavy chains, EP1395Y antibody (Abcam; 1:250, pretreatment with Tris buffer at 100 for 20 minutes), and the monoclonal antibody EMR8-5 (Abcam; 1:4000, pretreatment with citrate at 100 for 30 minutes) specific for heavy chains of human HLA class 1 A, -B, and -C as previously described. [20][21][22][23][24][25] Staining and expression patterns for all 4 tested antibodies were compared on a case-by-case basis by 3 independent observes (E.A., G.M., and V.H.K.) and found to be consistent ( Fig S2).…”

Section: Methodsmentioning

confidence: 99%

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

Koelzer

Dawson

Andersson

et al. 2015

Translational Research

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

Koelzer

Dawson

Andersson

et al. 2015

Translational Research

View full text Add to dashboard Cite

“…Neuronal expression of MHC-I in the human brain has only been reported in a small number of studies. The first was a study of a childhood viral infection, Rasmussen’s encephalitis, in which immunolabel for the MHC-I component, beta 2 microglobulin (β2m), was present in cortical and hippocampal neurons 20 ; more recently, MHC-I has also been observed in dysmorphic/dysphasic cortical neurons of focal cortical dysplasia, tuberous sclerosis complex and ganglioglioma cases 21 and in the embryonic LGN of the dorsal thalamus 22 and hippocampus 23 . In the LGN, β2m was observed at 29–31 gestational weeks but, was nearly absent by postnatal day 55, and was completely absent in the adult 22 .…”

Section: Introductionmentioning

confidence: 99%

MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

et al. 2014

View full text Add to dashboard Cite

Subsets of rodent neurons are reported to express major histocompatibilty complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression, and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell derived dopamine (DA) neurons. Catecholamine murine cultured neurons are more responsive to induction of MHC-I by gamma-interferon than other neuronal populations. Neuronal MHC-I is also induced by factors released from microglia activated by neuromelanin or alpha-synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize foreign ovalbumin and display antigen derived from this protein by MHC-I, which triggers DA neuronal death in the presence of appropriate cytotoxic T-cells. Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons may be particularly susceptible to T cell-mediated cytotoxic attack.

show abstract

“…We have proposed that this mechanism underlies the injury of demyelinated axons in multiple sclerosis (MS) 1, 2, 4, 10. Evidence also suggests that MHC I is involved with synaptic pruning during cortical development12, 13, 14, 16, 17, 18, 19, 20, 21 and following injury22, 23, 24, 25 and contributes to neuronal plasticity 16, 17, 26, 27. These findings also suggest that retrogradely induced MHC class I may contribute to the diffuse synaptopathy observed in MS and other neurodegenerative diseases 28, 29, 30, 31, 32, 33, 34, 35.…”

Section: Introductionmentioning

confidence: 99%

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Clarkson

Patel

LaFrance‐Corey

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveInjury‐associated axon‐intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen‐specific CD8+ T cells. We sought to determine whether the same is true in human neurons.MethodsA novel microisolation chamber design was used to physically isolate and manipulate axons from human skin fibroblast‐derived induced pluripotent stem cell (iPSC)‐derived neuron‐enriched neural aggregates. Fluorescent retrobeads were used to assess the fraction of neurons with projections to the distal chamber. Axons were treated with IFN γ for 72 h and expression of MHC class I and antigen presentation genes were evaluated by RT‐PCR and immunofluorescence.ResultsHuman iPSC‐derived neural stem cells maintained as 3D aggregate cultures in the cell body chamber of polymer microisolation chambers extended dense axonal projections into the fluidically isolated distal chamber. Treatment of these axons with IFN γ resulted in upregulation of MHC class I and antigen processing genes in the neuron cell bodies. IFN γ‐induced MHC class I molecules were also anterogradely transported into the distal axon.InterpretationThese results provide conclusive evidence that human axons are competent to express MHC class I molecules, suggesting that inflammatory factors enriched in demyelinated lesions may render axons vulnerable to attack by autoreactive CD8+ T cells in patients with MS. Future work will be aimed at identifying pathogenic anti‐axonal T cells in these patients.

show abstract

The spatio-temporal expression of MHC class I molecules during human hippocampal formation development

Cited by 26 publications

References 53 publications

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Contact Info

Product

Resources

About