Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D.
Minor histocompatibility Ags elicit cell-mediated immune responses and graft rejection in individuals receiving MHC-matched tissues. H60 represents a dominant Ag that elicits a strong CTL response in C57BL/6 mice immunized against BALB.B. An 8-aa peptide in the H60 protein is presented by H-2K(b) and this is recognized by the TCR as an alloantigen. The intact H60 glycoprotein is a ligand for the costimulatory NKG2D receptor that is expressed by activated CD8(+) T cells. Thus, H60 may provide both an allogeneic peptide and its own costimulation. We show that mutation of an H-2K(b)-binding anchor residue in the H60 peptide completely abrogates binding of H60 glycoprotein to NKG2D and a synthetic H60 peptide partially blocks the binding of NKG2D to its ligand. Ligands of the human NKG2D receptor are remarkably polymorphic, suggesting that these may also serve as minor histocompatibility Ags.
Cerwenka
Adelheid
A
Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
O'Callaghan
Christopher A
CA
Hamerman
Jessica A
JA
Yadav
Rajwardhan
R
Ajayi
Wilfred
W
Roopenian
Derry C
DC
Joyce
Sebastian
S
Lanier
Lewis L
LL
D000818:Animals; D017951:Antigen Presentation; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000378:metabolism* / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009842:Oligopeptides / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D012995:Solubility
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C114735:minor H antigen H60