title: Immunodominance of H60 is caused by an abnormally high precursor T cell pool directed against its unique minor histocompatibility antigen peptide.
abstract: The H60 minor histocompatibility (H) antigen peptide is derived from a glycoprotein that serves as a ligand for the stimulatory NKG2D receptor. We show that this peptide is remarkably immunodominant in that it competes effectively with MHC alloantigens, is efficiently crosspresented by host antigen-presenting cells (APCs), and readily elicits naive CD8 T cell responses in vitro. H60 immunodominance is neither a consequence of NKG2D engagement nor competition among minor H antigens on APCs. Instead, H60 immunodominance is a consequence of an abnormally high naive precursor frequency of H60 peptide reactive CD8 T cells. Understanding why the H60 peptide is so immunogenic has important implications in tissue transplantation and vaccine design.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Christianson
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sproule
authors.forename: Nadja
authors.initials: N
authors.lastname: Jung
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016056:Immunodominant Epitopes; D008024:Ligands; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D008912:Minor Histocompatibility Loci / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016377:Organ Transplantation; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014181:Transplantation Immunology
chemical_list: D016056:Immunodominant Epitopes; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C114735:minor H antigen H60