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 beta 2-microglobulin (beta 2mb) 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/beta 2ma). The fusion restored H-2Kb, Db and beta 2mb 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.
Ohlén
C
C
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Bastin
J
J
Ljunggren
H G
HG
Imreh
S
S
Klein
G
G
Townsend
A R
AR
Kärre
K
K
D000818:Animals; D005434:Flow Cytometry; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006822:Hybrid Cells; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007739:L Cells; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D001613:beta 2-Microglobulin