The H4(b) Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications.
Document Type
Article
Publication Date
2003
First Page
5133
Last Page
5142
JAX Source
J Immunol 2003 May; 170(10):5133-42.
Abstract
Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2K(b)-restricted epitope defining the mouse H4(b) minor H Ag. H4(b) is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4(b) but not the H4(a) epitope. Further, ex vivo CD8(+) T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings.
Recommended Citation
Yadav R,
Yoshimura Y,
Boesteanu A,
Christianson GJ,
Ajayi WU,
Shashidharamurthy R,
Stanic AK,
Roopenian DC,
Joyce S.
The H4(b) Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications. J Immunol 2003 May; 170(10):5133-42.