EPITOPE-SPECIFIC ENHANCEMENT OF ANTIGEN PRESENTATION BY INVARIANT CHAIN

The MHC class II-associated invariant chain (Ii) is involved in the in tracellular sorting of class II molecules to the endocytic pathway whe re peptides from processed exogenous antigens are bound, and thereby I i is thought to enhance antigen presentation. Here we demonstrate that presentation of only one out of five epitopes of a given antigen is a ugmented by li. We have compared the presentation of five different ep itopes derived from hen egg white lysozyme (HEL) to A(k)-restricted T hybridomas by rat-2 fibroblasts transfected with A(alpha)k and A(beta) k (RKK) and RKK cells supertransfected with the mouse invariant chain (RKKI). Only the presentation of the HEL epitope 46-61 was enhanced wh ereas the presentation of the HEL epitopes 25-43, 34-45, 112-124, and 116-129 was unchanged or even-slightly diminished in RKKI cells. The p resentation of the epitopes 25-43 and 34-45 was virtually insensitive to the lysosomotropic reagent chloroquine. Brefeldin A (BFA), which in hibits protein egress from the endoplasmic reticulum, blocked the pres entation of all epitopes tested in RKKI cells. In contrast, in Ii-nega tive RKK cells only the presentation of the epitope HEL(46-61) was inh ibited by BFA and the presentation of the epitopes 25-43 and 34-45 was only slightly impaired. These findings suggest that Ii may target cla ss II molecules to selected endosomal subcompartments involved in the processing of different peptides derived from an endocytosed antigen. As a result, the enhancement of the class II-restricted presentation i n Ii expressing cells appears to be epitope specific rather than antig en specific.