SELECTIVE PROCESSING OF EXOGENOUS ANTIGENS BY ANTIGEN-PRESENTING CELLS WITH DELETED MHC GENES

Recently, APCs expressing genes for the alpha- and beta-chains of MHC class II, but not other proteins encoded in the MHC class II locus, ha ve been found to be defective in processing proteins by the MHC class II Ag presentation pathway. Ag presentation of hen egg OVA has been ex amined in one of these cell lines, T2.A(k). OVA was processed normally by T2.A(k) when compared with OVA processed by T1.A(k), a cell line t hat expresses the MHC genes missing in T2.A(k). By contrast, native he n egg lysozyme (HEL) was not presented as Ag by T2.A(k), which is in a greement with earlier results. Digestion with thiol proteases is impor tant for Ag processing of HEL. We therefore analyzed the expression of these enzymes in T1.A(k) and T2.A(k) by using a reagent that specific ally radiolabels thiol proteases. In these experiments, the repertoire of proteases expressed in the microsomes of T1.A(k) was found to be d istinct from the repertoire expressed by T2.A(k). Finally, in in vitro digestion experiments, the group of thiol proteases active in T1.A(k) microsomes digested HEL differently from the group identified in T2.A (k). These results provide evidence that the defect in Ag presentation that is encoded by MHC genes and manifests itself in defective proces sing of HEL is not absolute. Further, the mutation in T2.A(k) coincide s with altered activities of thiol proteases, a class of enzymes invol ved in processing exogenous Ags.