A single nucleotide polymorphism in the Emp3 gene defines the H4 minor histocompatibility antigen. Immunogenetics 2003 Aug;55(5):284-95
Date
07/08/2003Pubmed ID
12845499DOI
10.1007/s00251-003-0581-xScopus ID
2-s2.0-0042330076 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Minor histocompatibility antigens (minor H antigen) elicit strong T-cell-mediated responses during both graft rejection and graft versus leukemia (GvL) among MHC-matched individuals (where MHC is major histocompatibility complex). Employing expression-cloning methodology, we have identified a cDNA clone, MI-35, encoding the immunodominant H4b minor H antigen within the classical mouse H4 complex. The minimal antigenic epitope derived from H4b presented on Kb class I MHC is SGIVYIHL (SYL8) and the polymorphism is due to C-->T nucleotide modification in p3 resulting in the change of threonine (ACT) to isoleucine (ATT). The results presented here demonstrate that amino acid variation in the allelic epitopes results in the low abundance of H4a peptide. The differential peptide copy number resulted in an immunodominant cytotoxic T cells (CTL) response directed against H4b while the anti-B6 response directed against H4a was easily dominated. These results provide a molecular mechanism for the H4 minor H antigen and suggest a novel mechanism by which alloantigenic disparity caused by conservative amino acid changes can be augmented by posttranslational antigen processing events.
Author List
Luedtke B, Pooler LM, Choi EY, Tranchita AM, Reinbold CJ, Brown AC, Shaffer DJ, Roopenian DC, Malarkannan SAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Chromosome Mapping
DNA, Complementary
Epitopes
Isoantigens
Membrane Glycoproteins
Mice
Minor Histocompatibility Antigens
Molecular Sequence Data
Polymorphism, Single Nucleotide