Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus

Bregje Mommaas, Janine Kamp, Jan Wouter Drijfhout, Nico Beekman, Ferry Ossendorp, Peter Van Veelen, Joke Den Haan, Els Goulmy, Tuna Mutis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA-1H and HA-1R, with a single amino acid difference. Whereas the immunogenicity of the HA-1R allele has not yet been shown, the nonameric HA-1H peptide induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known whether the mHag HA-1H or HA-1R associates with other HLA class I molecules. Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify HLA class I binding peptides that are properly processed by proteasomal degradation. Peptide binding analyses were performed for all nonameric HA-1H/R peptides for binding to nine HLA class I molecules with >10% prevalence in the Caucasian population and for seven nonameric/decameric HA-1H/R peptides predicted to bind to HLA-A3, -B14, and -B60 Only the nonameric KECVLH/RDDL and decameric KECVLH/RDDLL peptides showed strong and stable binding to HLA-B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1H and HA-1R peptides. In subsequent analyses, dendritic cells pulsed with the nonameric HA-1R peptide did not induce CTLs that recognize the natural HLA-B60/HA 1R ligand. In contrast, dendritic cells pulsed with the nonameric HA-1H peptide induced IFN-τ-secreting T cells specific for the natural HLA-B60/HA-1H ligand in three HLA-B60+HA-1RR individuals, demonstrating the immunogenicity of the HLA-B60/HA-1H ligand. In conclusion, this study shows a novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1 locus.

Original languageEnglish
Pages (from-to)3131-3136
Number of pages6
JournalJournal of Immunology
Volume169
Issue number6
DOIs
Publication statusPublished - 15 Sep 2002

Cite this

Mommaas, Bregje ; Kamp, Janine ; Drijfhout, Jan Wouter ; Beekman, Nico ; Ossendorp, Ferry ; Van Veelen, Peter ; Den Haan, Joke ; Goulmy, Els ; Mutis, Tuna. / Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus. In: Journal of Immunology. 2002 ; Vol. 169, No. 6. pp. 3131-3136.
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title = "Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus",
abstract = "The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA-1H and HA-1R, with a single amino acid difference. Whereas the immunogenicity of the HA-1R allele has not yet been shown, the nonameric HA-1H peptide induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known whether the mHag HA-1H or HA-1R associates with other HLA class I molecules. Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify HLA class I binding peptides that are properly processed by proteasomal degradation. Peptide binding analyses were performed for all nonameric HA-1H/R peptides for binding to nine HLA class I molecules with >10{\%} prevalence in the Caucasian population and for seven nonameric/decameric HA-1H/R peptides predicted to bind to HLA-A3, -B14, and -B60 Only the nonameric KECVLH/RDDL and decameric KECVLH/RDDLL peptides showed strong and stable binding to HLA-B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1H and HA-1R peptides. In subsequent analyses, dendritic cells pulsed with the nonameric HA-1R peptide did not induce CTLs that recognize the natural HLA-B60/HA 1R ligand. In contrast, dendritic cells pulsed with the nonameric HA-1H peptide induced IFN-τ-secreting T cells specific for the natural HLA-B60/HA-1H ligand in three HLA-B60+HA-1RR individuals, demonstrating the immunogenicity of the HLA-B60/HA-1H ligand. In conclusion, this study shows a novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1 locus.",
author = "Bregje Mommaas and Janine Kamp and Drijfhout, {Jan Wouter} and Nico Beekman and Ferry Ossendorp and {Van Veelen}, Peter and {Den Haan}, Joke and Els Goulmy and Tuna Mutis",
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Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus. / Mommaas, Bregje; Kamp, Janine; Drijfhout, Jan Wouter; Beekman, Nico; Ossendorp, Ferry; Van Veelen, Peter; Den Haan, Joke; Goulmy, Els; Mutis, Tuna.

In: Journal of Immunology, Vol. 169, No. 6, 15.09.2002, p. 3131-3136.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus

AU - Mommaas, Bregje

AU - Kamp, Janine

AU - Drijfhout, Jan Wouter

AU - Beekman, Nico

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AU - Goulmy, Els

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N2 - The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA-1H and HA-1R, with a single amino acid difference. Whereas the immunogenicity of the HA-1R allele has not yet been shown, the nonameric HA-1H peptide induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known whether the mHag HA-1H or HA-1R associates with other HLA class I molecules. Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify HLA class I binding peptides that are properly processed by proteasomal degradation. Peptide binding analyses were performed for all nonameric HA-1H/R peptides for binding to nine HLA class I molecules with >10% prevalence in the Caucasian population and for seven nonameric/decameric HA-1H/R peptides predicted to bind to HLA-A3, -B14, and -B60 Only the nonameric KECVLH/RDDL and decameric KECVLH/RDDLL peptides showed strong and stable binding to HLA-B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1H and HA-1R peptides. In subsequent analyses, dendritic cells pulsed with the nonameric HA-1R peptide did not induce CTLs that recognize the natural HLA-B60/HA 1R ligand. In contrast, dendritic cells pulsed with the nonameric HA-1H peptide induced IFN-τ-secreting T cells specific for the natural HLA-B60/HA-1H ligand in three HLA-B60+HA-1RR individuals, demonstrating the immunogenicity of the HLA-B60/HA-1H ligand. In conclusion, this study shows a novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1 locus.

AB - The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA-1H and HA-1R, with a single amino acid difference. Whereas the immunogenicity of the HA-1R allele has not yet been shown, the nonameric HA-1H peptide induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known whether the mHag HA-1H or HA-1R associates with other HLA class I molecules. Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify HLA class I binding peptides that are properly processed by proteasomal degradation. Peptide binding analyses were performed for all nonameric HA-1H/R peptides for binding to nine HLA class I molecules with >10% prevalence in the Caucasian population and for seven nonameric/decameric HA-1H/R peptides predicted to bind to HLA-A3, -B14, and -B60 Only the nonameric KECVLH/RDDL and decameric KECVLH/RDDLL peptides showed strong and stable binding to HLA-B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1H and HA-1R peptides. In subsequent analyses, dendritic cells pulsed with the nonameric HA-1R peptide did not induce CTLs that recognize the natural HLA-B60/HA 1R ligand. In contrast, dendritic cells pulsed with the nonameric HA-1H peptide induced IFN-τ-secreting T cells specific for the natural HLA-B60/HA-1H ligand in three HLA-B60+HA-1RR individuals, demonstrating the immunogenicity of the HLA-B60/HA-1H ligand. In conclusion, this study shows a novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1 locus.

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