The H4b minor histocompatibility antigen is caused by a combination of genetically determined and posttranslational modifications.

Yadav R, Yoshimura Y, Boesteanu A, Christianson GJ, Ajayi WU, Shashidharamurthy R, Stanic AK, Roopenian DC, Joyce S
J Immunol. 2003 170 (10): 5133-42

PMID: 12734360 · DOI:10.4049/jimmunol.170.10.5133

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.

MeSH Terms (22)

Amino Acid Substitution Animals Combinatorial Chemistry Techniques Conserved Sequence Epitopes, T-Lymphocyte H-2 Antigens Humans Immunodominant Epitopes Isoleucine Membrane Glycoproteins Membrane Proteins Mice Mice, Inbred BALB C Mice, Inbred C57BL Minor Histocompatibility Antigens Minor Histocompatibility Loci Molecular Mimicry Oligopeptides Peptide Library Phosphopeptides Protein Processing, Post-Translational Threonine

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