PMID- 12845499 OWN - NLM STAT- MEDLINE DCOM- 20031104 LR - 20181113 IS - 0093-7711 (Print) IS - 0093-7711 (Linking) VI - 55 IP - 5 DP - 2003 Aug TI - A single nucleotide polymorphism in the Emp3 gene defines the H4 minor histocompatibility antigen. PG - 284-95 AB - 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. FAU - Luedtke, Brianna AU - Luedtke B AD - Laboratory of Molecular Immunology, Blood Research Institute, Blood Center of South-eastern Wisconsin, Milwaukee, WI 53226-2178, USA. FAU - Pooler, Laura M AU - Pooler LM FAU - Choi, Eun Young AU - Choi EY FAU - Tranchita, Angela M AU - Tranchita AM FAU - Reinbold, Corbett J A AU - Reinbold CJ FAU - Brown, Aaron C AU - Brown AC FAU - Shaffer, Daniel J AU - Shaffer DJ FAU - Roopenian, Derry C AU - Roopenian DC FAU - Malarkannan, Subramaniam AU - Malarkannan S LA - eng GR - R01 AI28802/AI/NIAID NIH HHS/United States GR - R01 HL65479/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030704 PL - United States TA - Immunogenetics JT - Immunogenetics JID - 0420404 RN - 0 (DNA, Complementary) RN - 0 (EMP3 protein, human) RN - 0 (Emp3 protein, mouse) RN - 0 (Emp3 protein, rat) RN - 0 (Epitopes) RN - 0 (Isoantigens) RN - 0 (Membrane Glycoproteins) RN - 0 (Minor Histocompatibility Antigens) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Chromosome Mapping MH - DNA, Complementary MH - Epitopes MH - Isoantigens/genetics MH - Membrane Glycoproteins/*genetics MH - Mice MH - Minor Histocompatibility Antigens/*genetics MH - Molecular Sequence Data MH - *Polymorphism, Single Nucleotide EDAT- 2003/07/08 05:00 MHDA- 2003/11/05 05:00 CRDT- 2003/07/08 05:00 PHST- 2003/03/03 00:00 [received] PHST- 2003/05/12 00:00 [revised] PHST- 2003/07/08 05:00 [pubmed] PHST- 2003/11/05 05:00 [medline] PHST- 2003/07/08 05:00 [entrez] AID - 10.1007/s00251-003-0581-x [doi] PST - ppublish SO - Immunogenetics. 2003 Aug;55(5):284-95. doi: 10.1007/s00251-003-0581-x. Epub 2003 Jul 4.