The model B6dom1 minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene (original) (raw)
Abstract.
The B6dom1 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 B6dom1 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 STT3 gene. 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 B6dom1-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.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime Subscribe now
Buy Now
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Instant access to the full article PDF.
Similar content being viewed by others
Author information
Authors and Affiliations
- Department of Molecular Biology, Compatigene Inc., Montreal, Quebec, Canada, , , , ,
Kevin McBride, Serge Picard & Stéphanie Martin - Montreal Network for Pharmaco-Proteomics and Structural Genomics, Montreal, Quebec, Canada, , , , ,
Daniel Boismenu, Alex Bell & John Bergeron - Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, 5415 de l'Assomption Blvd, Montreal, Quebec, Canada H1T 2M4, , , , ,
Chantal Baron & Claude Perreault
Authors
- Kevin McBride
You can also search for this author inPubMed Google Scholar - Chantal Baron
You can also search for this author inPubMed Google Scholar - Serge Picard
You can also search for this author inPubMed Google Scholar - Stéphanie Martin
You can also search for this author inPubMed Google Scholar - Alex Bell
You can also search for this author inPubMed Google Scholar - John Bergeron
You can also search for this author inPubMed Google Scholar - Claude Perreault
You can also search for this author inPubMed Google Scholar
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
McBride, K., Baron, C., Picard, S. et al. The model B6dom1 minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene.Immunogenetics 54, 562–569 (2002). https://doi.org/10.1007/s00251-002-0502-4
- Received: 17 July 2002
- Revised: 22 August 2002
- Issue Date: November 2002
- DOI: https://doi.org/10.1007/s00251-002-0502-4