RESTORATION OF H-2B EXPRESSION AND PROCESSING OF ENDOGENOUS ANTIGENS IN THE MHC CLASS-I PATHWAY BY FUSION OF A LYMPHOMA MUTANT TO L-CELLS OF THE H-2K HAPLOTYPE

The RMA‐S lymphoma mutant cannot process and present antigens to H‐2‐restricted cytotoxic T lymphocytes. It synthesizes major histocompatibility complex class I heavy (H‐2KbDb) and light β2‐microglobulin (β2mb) chains of normal size and charge, but only a fraction of these assemble and reach the cell surface. As a first step investigating the genetic defect of this line, we have fused it to a L cell fibroblast line (H‐2KkDk/β2ma). The fusion restored H‐2Kb, Db and β2mb expression as well as the ability to process and present internally derived (minor histocompatibility and influenza virus nucleoprotein) antigens in RMA‐S. This shows that the mutation(s) responsible for the phenotype of RMA‐S is (are) not located within the MHC class I heavy and light chain genes. Other cellular factors, derived from the L cell fusion partner, can control antigen processing and transport of MHC class I molecules. These findings are discussed in relation to the observation that assembly and transport of MHC class I molecules can be induced in the mutant by H‐2b‐restricted peptides. The recessive nature of the defect and its independence of MHC class I genes in the mutant has important implications for future transfection studies, of this and similar mutants, aiming at establishing cells containing non‐assembled MHC class I molecules of different alleles and identifying the gene(s) controlling processing of endogenous antigens. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim