The model B6(dom1) minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene

The B6(dom1) minor histocompatibility antigen (MiHA) is a model antigen, since it is both the epitome of an immunodominant epitope and an ideal target for adoptive cancer immunotherapy. Based on DNA sequencing and MS/MS analyses, we report that B6(dom1) corresponds to amino acids 770-778 (KAPDNRETL)...

Full description

Saved in:
Bibliographic Details
Published in:Immunogenetics (New York) 2002-11, Vol.54 (8), p.562
Main Authors: McBride, Kevin, Baron, Chantal, Picard, Serge, Martin, Stéphanie, Boismenu, Daniel, Bell, Alex, Bergeron, John, Perreault, Claude
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cells, Cultured
Computational Biology
Cytotoxicity Tests, Immunologic
Genes, Fungal
Glycosyltransferases - chemistry
Glycosyltransferases - genetics
Glycosyltransferases - immunology
Hexosyltransferases
Humans
Immunodominant Epitopes - genetics
Immunodominant Epitopes - immunology
Mass Spectrometry
Membrane Proteins - genetics
Mice
Minor Histocompatibility Antigens - genetics
Molecular Sequence Data
Peptide Fragments - chemistry
Peptide Fragments - genetics
Peptide Fragments - immunology
Saccharomyces cerevisiae Proteins
Sequence Homology, Amino Acid
T-Lymphocytes, Cytotoxic - immunology
Yeasts - genetics
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The B6(dom1) minor histocompatibility antigen (MiHA) is a model antigen, since it is both the epitome of an immunodominant epitope and an ideal target for adoptive cancer immunotherapy. Based on DNA sequencing and MS/MS analyses, we report that B6(dom1) corresponds to amino acids 770-778 (KAPDNRETL) of a protein we propose to call SIMP (source of immunodominant MHC-associated peptides) that is encoded by a mouse homolog of the yeast STT3gene. STT3, a member of the oligosaccharyltransferase complex, is essential for cell proliferation. Phenotypic and genotypic analyses among eight strains of mice revealed a precise correlation between susceptibility or resistance to B6(dom1)-specific cytotoxic T lymphocytes (CTLs) and the presence of a Glu vs Asp amino acid at position 776 of the SIMP protein, respectively. Strikingly, while the difference in the amino acid sequence 770-778 encoded by the two SIMP alleles represents a very conservative substitution, these allelic peptides were not crossreactive at the CTL level, and both peptides were immunodominant when presented to mice homozygous for the opposite allele. In addition, we have cloned a human ortholog of SIMP whose predicted protein shares 97% amino acid identity with mouse SIMP. These results strengthen the concept that MHC class-I-associated MiHAs originate as a consequence of rare polymorphisms among highly conserved genes. Furthermore, the notion that a peptide differing from a self analog by a single methylene group can be immunodominant has implications regarding our understanding of the mechanisms of immunodominance.
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-002-0502-4