Functional requirement for class I MHC in CNS development and plasticity

Science. 2000 Dec 15;290(5499):2155-9. doi: 10.1126/science.290.5499.2155.

Abstract

Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a class I MHC receptor component, CD3zeta, refinement of connections between retina and central targets during development is incomplete. In the hippocampus of adult mutants, N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) is enhanced, and long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by distinct mosaics of neurons, reflecting a potential for diverse neuronal functions. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / physiology*
  • CD3 Complex / genetics
  • CD3 Complex / physiology*
  • Excitatory Postsynaptic Potentials
  • Gene Expression Profiling
  • Genes, MHC Class I
  • Geniculate Bodies / physiology
  • Hippocampus / growth & development
  • Hippocampus / physiology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / physiology*
  • In Situ Hybridization
  • Long-Term Potentiation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Neural Pathways
  • Neuronal Plasticity*
  • Neurons / physiology*
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Retina / growth & development
  • Retina / physiology
  • Retinal Ganglion Cells / physiology
  • Signal Transduction
  • Synapses / physiology*
  • Synaptic Transmission
  • Visual Pathways

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Histocompatibility Antigens Class I
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate