A single nucleotide polymorphism in the Emp3 gene defines the H4 minor histocompatibility antigen.
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.
Luedtke
Brianna
B
Laboratory of Molecular Immunology, Blood Research Institute, Blood Center of South-eastern Wisconsin, Milwaukee, WI 53226-2178, USA.
Pooler
Laura M
LM
Choi
Eun Young
EY
Tranchita
Angela M
AM
Reinbold
Corbett J A
CJ
Brown
Aaron C
AC
Shaffer
Daniel J
DJ
Roopenian
Derry C
DC
Malarkannan
Subramaniam
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary; D000939:Epitopes; D007519:Isoantigens / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
D018076:DNA, Complementary; C485157:EMP3 protein, human; C113389:Emp3 protein, mouse; C485158:Emp3 protein, rat; D000939:Epitopes; D007519:Isoantigens; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens