Single-residue changes in class I major histocompatibility complex molecules stimulate responses to self peptides.
Single-residue changes were introduced into the murine major histocompatibility complex class I molecule H-2Kb at positions 65 and 69, which are predicted to point up from the alpha-helix of the alpha 1 domain and not into the peptide binding groove. Mutated and wild-type genes were transfected into the murine cell line P815 (H-2d). We present evidence that the changes did not affect the binding of three foreign peptides that are recognized by cytotoxic T lymphocytes (CTL) in association with H-2Kb. Additionally, the mutants provoked strong alloreactive responses in T cells from mice expressing unmutated H-2Kb. The alloreactive CTL were specific for self peptides, which could be extracted from wild-type H-2Kb molecules, recognized in the context of the mutant class I.
Grandea
A G
AG
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Bevan
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D006183:H-2 Antigens / Q000737:chemistry / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D006183:H-2 Antigens; D007519:Isoantigens; D010047:Ovalbumin