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.
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.
Yadav, R; Yoshimura, Y; Boesteanu, A; Christianson, G J.; Ajayi, W U.; Shashidharamurthy, R; Stanic, A K.; Roopenian, D C.; and Joyce, S, " The H4(b) Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications." (2003). Faculty Research 2000 - 2009. 525.