title: Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen.
abstract: The K blood group remains an important target in hemolytic disease of the newborn (HDN), with no immune prophylaxis available. The aim was to characterize the Th response to K as a key step in designing specific immunotherapy and understanding the immunogenicity of the Ag. PBMCs from K-negative women who had anti-K Abs after incompatible pregnancy, and PBMCs from unimmunized controls, were screened for proliferative responses to peptide panels spanning the K or k single amino acid polymorphism. A dominant K peptide with the polymorphism at the C terminus elicited proliferation in 90% of alloimmunized women, and it was confirmed that responding cells expressed helper CD3(+)CD4(+) and "memory" CD45RO(+) phenotypes, and were MHC class II restricted. A relatively high prevalence of background peptide responses independent of alloimmunization may contribute to K immunogenicity. First, cross-reactive environmental Ag(s) pre-prime Kell-reactive Th cells, and, second, the K substitution disrupts an N-glycosylation motif, allowing the exposed amino acid chain to stimulate a Th repertoire that is unconstrained by self-tolerance in K-negative individuals. The dominant K peptide was effective in inducing linked suppression in HLA-transgenic mice and can now be taken forward for immunotherapy to prevent HDN because of anti-K responses.
authors.affiliation: Division of Applied Medicine, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Jillian
authors.initials: J
authors.lastname: Stephen
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Cairns
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Pickford
authors.forename: Mark A
authors.initials: MA
authors.lastname: Vickers
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Urbaniak
authors.forename: Robert N
authors.initials: RN
authors.lastname: Barker
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007626:Kell Blood-Group System / Q000737:chemistry / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011247:Pregnancy; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D007155:Immunologic Factors; D007626:Kell Blood-Group System; D010455:Peptides