Chlamydial infection and the efficiency of MHC class I self-antigen presentation in a lymphoblastoid cell line

Abstract

Abstract The direct MHC class I antigen presentation pathway presents cytosolic proteins for immune surveillance. While this pathway is an attractive target for therapeutics, we must first understand the efficiency of antigen presentation. Previous studies have shown the presentation efficiency from pathogen-derived antigens ranges from 0.03–25%. The intracellular lifestyle of Chlamydia makes them an attractive model to study class I presentation. It is likely that Chlamydia have developed mechanisms to evade CD8+ T cells through manipulation of this pathway. Here, we investigate the impact of Chlamydial infection on a recombinant fusion protein expressed in a human lymphoblastoid cell line (JY). The fusion protein contains a destabilization domain, an antigenic peptide, and a reporter. Chlamydial infection led to decreased accumulation of the model protein and increased presentation of model protein-derived antigens. This enhanced self-peptide presentation was only observed when antigen presentation was restricted to the DRiP form of the protein. We also investigated the antigen presentation efficiency of different model recombinant proteins in JY cells. We calculated the antigen presentation efficiency to be 0.35%, much lower than was previously observed in murine cells with a similar protein. The skewed antigen presentation phenotype observed following Chlamydial infection was not statistically different from the efficiency observed in the absence of infection. These data suggest that Chlamydia have evolved a mechanism to skew the host antigen presentation machinery toward presentation of DRiPs, and that the efficiency of direct class I presentation may be mechanistically unique among common immune signaling pathways.