Resistance to H-2-restricted but not to allo-H2-specific graft and cytotoxic T lymphocyte responses in lymphoma mutant.
The lymphoma mutant RMA-S escaped graft rejection after transplantation over a minor histocompatibility barrier, whereas it was rejected in H-2 allogeneic mice. The parental control line was rejected in both situations. The mutant, which had been selected against MHC class I molecules retained 5 to 10% of the wild-type H-2Db, Kb, and beta 2-microglobulin expression on the cell surface. It remained sensitive to allo-H-2b CTL in vitro, but was completely resistant to minor histocompatibility antigen-specific, H-2b-restricted CTL. It was equally resistant to other H-2b-restricted responses against internally derived Ag, such as tumor-specific CTL or a CTL clone specific for the influenza virus nucleoprotein. The results indicate a target cell defect that selectively abolishes the sensitivity to H-2-restricted CTL directed against internally processed Ag. This appears sufficient to shift the transplantation response over a minor histocompatibility Ag barrier from rejection to acceptance. There are two possible explanations for the results: 1) a block in the MHC class I-directed pathway for internal Ag processing, and 2) subthreshold H-2/Ag ligand density in relation to triggering requirements of restricted CTL. Regardless of the type of defect, the results demonstrate a difference between allo-H-2-specific and H-2-restricted CTL recognition at the level of the target cell.
Ohlén
C
C
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Bastin
J
J
Ljunggren
H G
HG
Foster
L
L
Wolpert
E
E
Klein
G
G
Townsend
A R
AR
Kärre
K
K
D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006084:Graft Rejection; D006183:H-2 Antigens / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex; D008912:Minor Histocompatibility Loci; D009154:Mutation; D009368:Neoplasm Transplantation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins; D014764:Viral Proteins / Q000276:immunology
D006183:H-2 Antigens; D006649:Histocompatibility Antigens; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins