title: A splice variant of HLA-A with a deletion of exon 3 expressed as nonmature cell-surface glycoproteins forms a heterodimeric structure with full-length HLA-A.
abstract: Alternatively spliced isoforms of the major histocompatibility complex (MHC) class I genes have been reported in many different species and therefore alternative splicing has been observed to be an additional layer of diversity in the MHC class I region. Here we show the characterization of a HLA-A splice variant in the human peripheral blood mononuclear cells (named "HLA-AΔE3"). This transcript is characterized by the deletion of exon 3 that encodes the α2 domain of the full-length HLA-A protein. Cell surface biotinylation experiments indicated that HLA-AΔE3 is able to be transported to the cell surface, as a 34-KDa glycoprotein that is totally sensitive to endoglycosidase-H treatment. Under nonreducing conditions, HLA-AΔE3 can form disulfide-linked homodimers on the cell surface. Furthermore, co-immunoprecipitation studies revealed that HLA-AΔE3 could interact with full-length HLA-A, forming a heterodimeric complex. These findings suggest that the splice variants of HLA-A under steady-state conditions may have an important function in regulating immune homeostasis.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
authors.forename: Zheng-Xi
authors.initials: ZX
authors.lastname: Dai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
authors.forename: Gao-Hong
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Xi-He
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Jia-Wu
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China. Electronic address: zhengyt@mail.kiz.ac.cn.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D019281:Dimerization; D005091:Exons / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D020033:Protein Isoforms