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SNP in exon 2 of the MUC1 gene generates a candidate minor histocompatibility antigen through alternative splicing
Author(s) -
Zhang Lixin,
Finn Olivera J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.22
Subject(s) - muc1 , exon , biology , genetics , single nucleotide polymorphism , minor histocompatibility antigen , human leukocyte antigen , minor allele frequency , microbiology and biotechnology , alternative splicing , gene , epitope , major histocompatibility complex , antigen , genotype
Minor histocompatibility antigens (mHAg's) are allelic peptides encoded by polymorphic genes that can bind MHCI or II molecules and initiate an immune response in allele‐negative hosts. MUC1 is a type I transmembrane glycoprotein with variable numbers of tandem repeats (VNTRs) and aberrant expression in many tumors makes it an ideal target for cancer therapy. MUC1 is polymorphic not only in the VNTR region but also in sequences outside of the VNTR. At least 33 single nucleotide polymorphisms (SNPs) in the MUC1 gene have been reported, one of which is a 3506 G/A SNP located in the exon 2. In the 54 MUC1 isoforms we recently isolated, 27 isoforms have 3506 G while the other half have 3506 A SNPs. The 3506 G allele encodes a 27‐bp additional sequence from 3' end of intron 1 that encodes a 9 a.a. peptide, which theoretically affects the cleavage site selection of the signal peptide by adding 10 a.a. to the N‐terminus of the mature proteins. Three peptides were synthesized according to the epitope prediction results and MHCI stabilization assay showed that they could bind HLA‐A0201 as well as H‐2Kb . In vivo assay are being done now in MUC1.Tg mice. This MUC1 minor antigen may serve as a new target for tumor immunotherapy. Supported by NIH grant RO1CA56103.