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
A. Oxenius et al., 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, European Journal of Immunology, 25(12), 1995, pp. 3402-3411
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.