Biochemical and immunogenetic analysis of an immunodominant peptide (B6dom1) encoded by the classical H7 minor histocompatibility locus

PA Eden, GJ Christianson, P Fontaine… - The Journal of …, 1999 - journals.aai.org
PA Eden, GJ Christianson, P Fontaine, PJ Wettstein, C Perreault, DC Roopenian
The Journal of Immunology, 1999journals.aai.org
Of the many minor histocompatibility (H) Ags that have been detected in mice, the ability to
induce graft vs host disease (GVHD) after bone marrow transplantation is restricted to a
limited number of immunodominant Ags. One such murine Ag, B6 dom1, is presented by the
H2-D b MHC class I molecule. We present biochemical evidence that the natural B6 dom1
peptide is indistinguishable from AAPDNRETF, and we show that this peptide can be
isolated from a wide array of tissues, with highest levels from the lymphoid organs and lung …
Abstract
Of the many minor histocompatibility (H) Ags that have been detected in mice, the ability to induce graft vs host disease (GVHD) after bone marrow transplantation is restricted to a limited number of immunodominant Ags. One such murine Ag, B6 dom1, is presented by the H2-D b MHC class I molecule. We present biochemical evidence that the natural B6 dom1 peptide is indistinguishable from AAPDNRETF, and we show that this peptide can be isolated from a wide array of tissues, with highest levels from the lymphoid organs and lung. Moreover, we employ a novel, somatic cell selection technique involving CTL-mediated immunoselection coupled with classical genetics, to show that B6 dom1 is encoded by the H7 minor H locus originally discovered∼ 40 years ago. These studies provide a molecular genetic framework for understanding B6 dom1, and exemplify the fact that mouse minor H loci that encode immunodominant CTL epitopes can correspond to classical H loci originally identified by their ability to confer strong resistance to tumor transplantation. Additionally, these studies demonstrate the utility of somatic cell selection approaches toward resolving H Ag immunogenetics.
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