Functional Requirement for Class I MHC in CNS Development and Plasticity

• Published in: Science (American Association for the Advancement of Science) 2000-12, Vol.290 (5499), p.2155-2159
• Main Authors: Huh, Gene S., Boulanger, Lisa M., Du, Hongping, Riquelme, Patricio A., Brotz, Tilmann M., Shatz, Carla J.
• Format: Article
• Language: English
• Subjects: Analysis; Anatomy; Animals; Antigens; Biochemistry; Biological and medical sciences; Biotechnology industries; Biotechnology industry; Brain - growth & development; Brain - physiology; CD3 antigen; CD3 Complex - genetics; CD3 Complex - physiology; CD3^Q antigen; Central nervous system; Excitatory Postsynaptic Potentials; Eyes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Profiling; Genes, MHC Class I; Genetics; Geniculate Bodies - physiology; Genotypes; Hippocampus; Hippocampus - growth & development; Hippocampus - physiology; Histocompatibility antigens (hla, h-2 and other systems); Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - physiology; In Situ Hybridization; Long term potentiation; Major histocompatibility complex; Messenger RNA; Methods; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Molecular immunology; Molecules; Neural Pathways; Neurology; Neuronal Plasticity; Neurons; Neurons - physiology; Proteins; Receptors, GABA-A - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Retina - growth & development; Retina - physiology; Retinal Ganglion Cells - physiology; Rodents; Signal Transduction; Synapses; Synapses - physiology; Synaptic Transmission; Vision research; Visual Pathways
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5499.2155

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).