PRESENTATION OF VIRAL-ANTIGENS RESTRICTED BY H-2K(B), D-B OR K-D IN PROTEASOME SUBUNIT LMP2-DEFICIENT AND LMP7-DEFICIENT CELLS

In the class II region of the major histocompatibility complex (MHC), four genes implicated in MHC class I-mediated antigen processing have been described. Two genes (TAP 1 and TAP 2) code for multimembrane-spa nning ATP-binding transporter proteins and two genes (LMP 2 and LMP 7) code for subunits of the proteasome. While TAP 1 and TAP 2 have been shown to transport antigenic peptides from the cytosol into the endopl asmic reticulum, where the peptides associate with MHC class I molecul es, the role of LMP 2/7 in antigen presentation is less clear. Using a ntigen processing mutant T2 cells that lack TAP 1/2 and LMP 2/7 genes, it was recently shown that expression of TAP 1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA-2 by HLA-A2. To under stand if presentation of a broader range of viral antigens occurs in t he absence of LMP 2/7, we transfected T2 cells with TAP 1, TAP 2 and e ither of the H-2K(b), D-b or K-d genes and tested their ability to pre sent vesicular stomatitis vires and influenza virus antigens to virus- specific cytotoxic T lymphocytes. We found that T2 cells, expressing T AP 1/2 gene products, presented all tested viral antigens restricted t hrough either the H-2K(b), D-b or K-d class I molecules. We conclude t hat the proteasome subunits LMP 2/7 as well as other gene products in the MHC class Il region, except from TAP 1/2, are not generally necess ary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP 2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.