Skip to main content
SpringerLink
Log in

The Expression Patterns of MHC Class I Molecules in the Developmental Human Visual System

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

It has been considered that healthy neurons in central nervous system (CNS) do not express major histocompatibility complex (MHC) class I molecules. However, recent studies clearly demonstrated the expression of functional MHC class I in the mammalian embryonic, neonatal and adult brain. Until now, it is still unknown whether MHC I molecules are expressed in the development of human brain. We collected nine human brain tissues from fetuses aged from 21 to 31 gestational weeks (GW), one newborn of postnatal 55 days and one adult. The expression of MHC class I molecules was detected during the development of visual system in human brain by immunohistochemistry and immunofluorescence. MHC class I proteins were located at lateral geniculate nucleus (LGN) and the expression was gradually increased from 21 GW to 31 GW and reached high levels at 30–31 GW when fine-scale refinement phase was mediated by neural electric activity. However, there was no expression of MHC class I molecules in the visual cortical cortex during all the developmental stages examined. We also concluded that MHC class I molecules were mainly expressed in neurons but not in astrocytes at LGN. In the developing visual system, the expression of β2M protein on neurons was not found in our study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bjorkman PJ, Parham P (1990) Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem 59:253–288

    Article  PubMed  CAS  Google Scholar 

  2. Amadou C (1999) Evolution of the MHC class I region: the framework hypothesis. Immunogenetics 49(4):362–367

    Article  PubMed  CAS  Google Scholar 

  3. Aarli JA (1983) The immune system and the nervous system. J Neurol 229(3):137–154

    Article  PubMed  CAS  Google Scholar 

  4. Wong GH, Bartlett PF, Clark-Lewis I et al (1984) Inducible expression of H-2 and Ia antigens on brain cells. Nature 310(5979):688–691

    Article  PubMed  CAS  Google Scholar 

  5. Joly E, Mucke L, Oldstone MB (1991) Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science 253(5025):1283–1285

    Article  PubMed  CAS  Google Scholar 

  6. Neumann H, Cavalie A, Jenne DE et al (1995) Induction of MHC class I genes in neurons. Science 269(5223):549–552

    Article  PubMed  CAS  Google Scholar 

  7. Neumann H, Schmidt H, Cavalie A et al (1997) Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. J Exp Med 185(2):305–316

    Article  PubMed  CAS  Google Scholar 

  8. Kimura T, Griffin DE (2000) The role of CD8(+) T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent sindbis virus. J Virol 74(13):6117–6125

    Article  PubMed  CAS  Google Scholar 

  9. Corriveau RA, Huh GS, Shatz CJ (1998) Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron 21(3):505–520

    Article  PubMed  CAS  Google Scholar 

  10. Huh GS, Boulanger LM, Du H et al (2000) Functional requirement for class I MHC in CNS development and plasticity. Science 290(5499):2155–2159

    Article  PubMed  CAS  Google Scholar 

  11. Oliveira AL, Thams S, Lidman O et al (2004) A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proc Natl Acad Sci USA 101(51):17843–17848

    Article  PubMed  CAS  Google Scholar 

  12. Ribic A, Flugge G, Schlumbohm C et al (2011) Activity-dependent regulation of MHC class I expression in the developing primary visual cortex of the common marmoset monkey. Behav Brain Funct 7:1

    Article  PubMed  CAS  Google Scholar 

  13. Linda H, Hammarberg H, Piehl F et al (1999) Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons. J Neuroimmunol 101(1):76–86

    Article  PubMed  CAS  Google Scholar 

  14. McConnell MJ, Huang YH, Datwani A et al (2009) H2-K(b) and H2-D(b) regulate cerebellar long-term depression and limit motor learning. Proc Natl Acad Sci USA 106(16):6784–6789

    Article  PubMed  CAS  Google Scholar 

  15. Needleman LA, Liu XB, El-Sabeawy F et al (2010) MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood. Proc Natl Acad Sci USA 107(39):16999–17004

    Article  PubMed  CAS  Google Scholar 

  16. Glynn MW, Elmer BM, Garay PA et al (2011) MHCI negatively regulates synapse density during the establishment of cortical connections. Nat Neurosci 14(4):442–451

    Article  PubMed  CAS  Google Scholar 

  17. Hitchcock PF, Hickey TL (1980) Prenatal development of the human lateral geniculate nucleus. J Comp Neurol 194(2):395–411

    Article  PubMed  CAS  Google Scholar 

  18. Stam NJ, Spits H, Ploegh HL (1986) Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 137(7):2299–2306

    PubMed  CAS  Google Scholar 

  19. Ellis SA, Strachan T, Palmer MS et al (1989) Complete nucleotide sequence of a unique HLA class I C locus product expressed on the human choriocarcinoma cell line BeWo. J Immunol 142(9):3281–3285

    PubMed  CAS  Google Scholar 

  20. Hutter H, Hammer A, Blaschitz A et al (1996) Expression of HLA class I molecules in human first trimester and term placenta trophoblast. Cell Tissue Res 286(3):439–447

    Article  PubMed  CAS  Google Scholar 

  21. Stam NJ, Vroom TM, Peters PJ et al (1990) HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol 2(2):113–125

    Article  PubMed  CAS  Google Scholar 

  22. Tsukahara T, Kawaguchi S, Torigoe T et al (2006) Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5. Cancer Sci 97(12):1374–1380

    Article  PubMed  CAS  Google Scholar 

  23. Williams DB, Barber BH, Flavell RA et al (1989) Role of beta 2-microglobulin in the intracellular transport and surface expression of murine class I histocompatibility molecules. J Immunol 142(8):2796–2806

    PubMed  CAS  Google Scholar 

  24. Spiliotis ET, Pentcheva T, Edidin M (2002) Probing for membrane domains in the endoplasmic reticulum: retention and degradation of unassembled MHC class I molecules. Mol Biol Cell 13(5):1566–1581

    Article  PubMed  CAS  Google Scholar 

  25. Schnabl E, Stockinger H, Majdic O et al (1990) Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin. J Exp Med 171(5):1431–1442

    Article  PubMed  CAS  Google Scholar 

  26. Madrigal JA, Belich MP, Benjamin RJ et al (1991) Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells. J Exp Med 174(5):1085–1095

    Article  PubMed  CAS  Google Scholar 

  27. Demaria S, Schwab R, Bushkin Y (1992) The origin and fate of beta 2 m-free MHC class I molecules induced on activated T cells. Cell Immunol 142(1):103–113

    Article  PubMed  CAS  Google Scholar 

  28. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116(1):201–211

    PubMed  CAS  Google Scholar 

  29. Wolf HK, Buslei R, Schmidt-Kastner R et al (1996) NeuN: a useful neuronal marker for diagnostic histopathology. J Histochem Cytochem 44(10):1167–1171

    Article  PubMed  CAS  Google Scholar 

  30. Sarnat HB, Nochlin D, Born DE (1998) Neuronal nuclear antigen (NeuN): a marker of neuronal maturation in early human fetal nervous system. Brain Dev 20(2):88–94

    Article  PubMed  CAS  Google Scholar 

  31. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: gFAP-thirty-one years (1969–2000). Neurochem Res 25(9–10):1439–1451

    Article  PubMed  CAS  Google Scholar 

  32. Antonini A, Fagiolini M, Stryker MP (1999) Anatomical correlates of functional plasticity in mouse visual cortex. J Neurosci 19(11):4388–4406

    PubMed  CAS  Google Scholar 

  33. Kumanovics A, Takada T, Lindahl KF (2003) Genomic organization of the mammalian MHC. Annu Rev Immunol 21:629–657

    Article  PubMed  CAS  Google Scholar 

  34. Datwani A, McConnell MJ, Kanold PO et al (2009) Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity. Neuron 64(4):463–470

    Article  PubMed  CAS  Google Scholar 

  35. Shatz CJ (1983) The prenatal development of the cat’s retinogeniculate pathway. J Neurosci 3(3):482–499

    PubMed  CAS  Google Scholar 

  36. Hevner RF (2000) Development of connections in the human visual system during fetal mid-gestation: a DiI-tracing study. J Neuropathol Exp Neurol 59(5):385–392

    PubMed  CAS  Google Scholar 

  37. Godement P, Salaun J, Imbert M (1984) Prenatal and postnatal development of retinogeniculate and retinocollicular projections in the mouse. J Comp Neurol 230(4):552–575

    Article  PubMed  CAS  Google Scholar 

  38. Rakic P (1976) Prenatal genesis of connections subserving ocular dominance in the rhesus monkey. Nature 261(5560):467–471

    Article  PubMed  CAS  Google Scholar 

  39. Rakic P (1977) Prenatal development of the visual system in rhesus monkey. Philos Trans R Soc Lond B Biol Sci 278(961):245–260

    Article  PubMed  CAS  Google Scholar 

  40. Graven SN (2004) Early neurosensory visual development of the fetus and newborn. Clin Perinatol 31(2):199–216

    Article  PubMed  Google Scholar 

  41. Huberman AD (2007) Mechanisms of eye-specific visual circuit development. Curr Opin Neurobiol 17(1):73–80

    Article  PubMed  CAS  Google Scholar 

  42. Solheim JC (1999) Class I MHC molecules: assembly and antigen presentation. Immunol Rev 172:11–19

    Article  PubMed  CAS  Google Scholar 

  43. Cresswell P, Ackerman AL, Giodini A et al (2005) Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 207:145–157

    Article  PubMed  CAS  Google Scholar 

  44. Arosa FA, Santos SG, Powis SJ (2007) Open conformers: the hidden face of MHC-I molecules. Trends Immunol 28(3):115–123

    Article  PubMed  CAS  Google Scholar 

  45. Allen H, Fraser J, Flyer D et al (1986) Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proc Natl Acad Sci USA 83(19):7447–7451

    Article  PubMed  CAS  Google Scholar 

  46. Fishman D, Elhyany S, Segal S (2004) Non-immune functions of MHC class I glycoproteins in normal and malignant cells. Folia Biol (Praha) 50(2):35–42

    CAS  Google Scholar 

  47. Torres AR, Sweeten TL, Cutler A et al (2006) The association and linkage of the HLA-A2 class I allele with autism. Hum Immunol 67(4–5):346–351

    Article  PubMed  CAS  Google Scholar 

  48. Stefansson H, Ophoff RA, Steinberg S et al (2009) Common variants conferring risk of schizophrenia. Nature 460(7256):744–747

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Nature Science Foundation of China (31070807, 31100649) and Research Fund for the Doctoral Program of Higher Education of China (20100092110040).

Author information

Authors and Affiliations

  1. Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China

    Aifeng Zhang, Yuqing Shen, Jiane Liu, Youji He, Qian Shi, Bo Fu, Fengqin Miao & Jianqiong Zhang

  2. Department of Pathology, Medical School, Southeast University, Nanjing, China

    Aifeng Zhang

  3. Department of Obstetrics and Gynecology, Zhongda Hospital Affiliated to Southeast University, Nanjing, China

    Hong Yu

Authors
  1. Aifeng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuqing Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiane Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youji He
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qian Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bo Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fengqin Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jianqiong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianqiong Zhang.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, A., Yu, H., Shen, Y. et al. The Expression Patterns of MHC Class I Molecules in the Developmental Human Visual System. Neurochem Res 38, 273–281 (2013). https://doi.org/10.1007/s11064-012-0916-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0916-9

Keywords

Search

Navigation