The proteasome regulator PA28α/β can enhance antigen presentation without affecting 20S proteasome subunit composition

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Abstract
PA28α/β is a regulatory complex of the 20S proteasome which consists of two IFN‐γ inducible subunits. Both subunits, α and β, contribute equally to the formation of hexa‐ or heptameric rings which can associate with the 20S proteasome. Previously, we have shown that overexpression of the PA28α subunit enhanced the MHC class I‐restricted presentation of two viral epitopes and that purified PA28α/β accelerated T cell epitope generation by the 20S proteasome in vitro, indicating a role for PA28α/β in antigen presentation. This conclusion was recently confirmed in PA28β gene targeted mice which were severely deficient in MHC class I‐restricted antigen presentation. These mice displayed a defect in the assembly of immunoproteasomes, suggesting that a lack of the proteasome subunits LMP2, LMP7, and MECL‐1 may account for the deficiency in antigen presentation. In this study we investigated whether the effect of PA28α/β on antigen presentation is dependent on a change of proteasome subunit composition. We have analyzed the assembly and subunit composition of proteasomes in fibroblast transfectants overexpressing both, α and β subunits of PA28. In these transfectants we found a marked enhancement in the presentation of the immunodominant H‐2Ld‐restricted pp89 epitope of murine cytomegalovirus, although the 20S proteasome composition was the same as in recipient cells. We, therefore, conclude that PA28α/β can enhance antigen processing independently of changes in 20S proteasome subunit composition or assembly.