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Functional Requirement for Class I MHC in CNS Development and Plasticity
Gene S. Huh,*Lisa M. Boulanger,Hongping Du,Patricio A. Riquelme,Tilmann M. Brotz,Carla J. Shatz*
Class I major histocompatibility complex (class I MHC)
molecules, known to be important for immune responses to antigen, areexpressed also by neurons that undergo activity-dependent, long-termstructural and synaptic modifications. Here, we show that in micegenetically deficient for cell surface class I MHC or for a classI MHC
receptor component, CD3, refinement of connections betweenretina
and central targets during development is incomplete. Inthe
hippocampus of adult mutants,
N-methyl-D-aspartate receptor-dependentlong-term potentiation (LTP) is enhanced, and long-term depression(LTD) is absent. Specific class I MHC messenger RNAs are expressedby
distinct mosaics of neurons, reflecting a potential for diverseneuronal functions. These results demonstrate an important rolefor
these molecules in the activity-dependent remodeling and plasticityof
connections in the developing and mature mammalian centralnervous
system (CNS).
Department of Neurobiology, Harvard Medical School, 220 Longwood
Avenue, Boston, MA 02115, USA.
*
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, Room4B36, Bethesda, MD 20892, USA.
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