PRESENTATION OF ENDOGENOUS VIRAL-PROTEINS IN ASSOCIATION WITH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II - ON THE ROLE OF INTRACELLULAR COMPARTMENTALIZATION, INVARIANT CHAIN AND THE TAP TRANSPORTER SYSTEM

Major histocompatibility complex (MHC) class II-associated antigen pre sentation is mainly linked to processing of exogenous antigens upon ce llular uptake by endocytosis, but has also been observed for endogenou sly sythesized antigens. We have studied the MHC class II-associated p resentation of the endogenously synthesized membrane associated glycop rotein (GP) and the cytosolic nucleoprotein (NP) of lymphocytic chorio meningitis virus (LCMV) in professional antigen presenting cells (APC) of mice. Since LCMV is a noncytopathic virus and minimally affects ce llular protein synthesis, it is a convenient virus for the study of an tigen presentation. In contrast, most other studies assessing class II -associated presentation of endogeneously synthesized viral antigens u sed cytolytic viruses such as vaccinia, measles and influenza virus, w hich drastically interfere with host cell functions. In addition, most studies were performed using non-professional APC. We found that clas s II-associated presentation of endogenously synthesized membrane asso ciated LCMV-GP was efficient and could not be inhibited by chloroquine or leupeptin. Neither the transporter associated with professing (TAP ) system nor the invariant chain (Ii) were significantly involved in t his process. In contrast, MHC class II-associated presentation of endo genously synthesized cytosolic LCMV-NP was not observed even in Ii-def icient APC. Thus, MHC class II loading of endogenously synthesized LCM V-GP apparently does not require processing in acidic endosomal compar tments as defined by chloroquine and leupeptin insensitivity Furthermo re, although the TAP molecules transport peptides of up to 15 amino ac ids in length, which potentially could bind to MHC class II molecules in the endoplasmic reticulum, such a process apparently does not occur for either the glycoprotein or the nucleoprotein. Therefore, the subc ellular localization of an endogenously synthesized protein influences crucially whether or not MHC class II loading can occur independently of the acidic compartments usually involved in MHC class II loading.