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Functional Requirement for Class I MHC in CNS Development and Plasticity

Science  15 Dec 2000:
Vol. 290, Issue 5499, pp. 2155-2159
DOI: 10.1126/science.290.5499.2155

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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, CD3ζ, 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).

  • * To whom correspondence may be addressed. E-mail: gshuh{at}alum.mit.edu or carla_shatz{at}hms.harvard.edu

  • Present address: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 4B36, Bethesda, MD 20892, USA.

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