ASTROCYTES EXPRESS ELEMENTS OF THE CLASS-II ENDOCYTIC PATHWAY AND PROCESS CENTRAL-NERVOUS-SYSTEM AUTOANTIGEN FOR PRESENTATION TO ENCEPHALITOGENIC T-CELLS

Astrocytes are nonprofessional APCs that may participate in Ag present ation and activation of pathogenic CD4(+) T cells involved in central nervous system (CNS) inflammatory diseases. Using immortalized pure as trocytes as a complement to the study of primary astrocytes, we invest igated whether these astrocytes express elements involved in the class II endocytic pathway and if they are capable of processing native mye lin basic protein (MBP), a step that could be necessary for initiating or perpetuating T cell recognition of this self-hg in vivo. Upon IFN- gamma-stimulation, primary and immortalized astrocytes up-regulate cla ss II transactivator (CIITA), invariant Chain (Ii) (p31 and p41), H-2M a, and H-2Mb Analysis of CIITA cDNA sequences demonstrated that CIITA transcription in astrocytes is directed by a promoter (type IV) that m ediates IFN-gamma-inducilble CIITA expression and encodes a CIITA prot ein that differs in its N-terminal sequence from CIITA reported in pro fessional APC, Comparing live and fixed APC for Ag presentation, we sh ow that Ag processing by APC is required for presentation of native MB P to antopathogenic T cells specific for the major MBP epitope, Ac1-11 , We have observed that primary astrocytes and some, but not all, astr ocyte lines in the absence of contaminating microglia are capable of p rocessing and presenting native MBP, suggesting that there may be hete rogeneity. Our study provides definitive evidence that astrocytes are capable of processing CNS autoantigen, indicating that astrocytes have potential for processing and presentation of CNS autoantigen to proin flammatory T cells in CNS autoimmune disease.