Identification of an immunodominant mouse minor histocompatibility antigen (MiHA). T cell response to a single dominant MiHA causes graft-versus-host disease.
T cell responses to non-MHC antigens are targeted to a restricted number of immunodominant minor histocompatibility antigens whose identity remains elusive. Here we report isolation and sequencing of a novel immunodominant minor histocompatibility antigen presented by H-2Db on the surface of C57BL/6 mouse cells. This nonapeptide (AAPDNRETF) shows strong biologic activity in cytotoxic T lymphocyte sensitization assays at concentrations as low as 10 pM. C3H.SW mice primed with AAPDNRETF in incomplete Freund's adjuvant generated a potent anti-C57BL/6 T cell-mediated cytotoxic activity, and T lymphocytes from AAPDNRETF-primed mice caused graft-versus-host disease when transplanted in irradiated C57BL/6 recipients. These results (a) provide molecular characterization of a mouse dominant minor histocompatibility antigen, (b) identify this peptide as a potential target of graft-versus-host disease and, (c) more importantly, demonstrate that a single dominant minor antigen can cause graft-versus-host disease. These findings open new avenues for the prevention of graft-versus-host disease and should further our understanding of the mechanisms of immunodominance in T cell responses to minor histocompatibility antigens.
Perreault
C
C
Department of Medicine, University of Montreal, Quebec, Canada. perreauc@ere.umontreal.ca
Jutras
J
J
Roy
D C
DC
Filep
J G
JG
Brochu
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D006086:Graft vs Host Disease / Q000209:etiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000032:analysis*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015778:Minor Histocompatibility Antigens