title: The β2-microglobulin-free heterodimerization of rhesus monkey MHC class I A with its normally spliced variant reduces the ubiquitin-dependent degradation of MHC class I A.
abstract: The MHC class I (MHC I) molecules play a pivotal role in the regulation of immune responses by presenting antigenic peptides to CTLs and by regulating cytolytic activities of NK cells. In this article, we show that MHC I A in rhesus macaques can be alternatively spliced, generating a novel MHC I A isoform (termed "MHC I A-sv1") devoid of α(3) domain. Despite the absence of β2-microglobulin (β2m), the MHC I A-sv1 proteins reached the cell surface of K562-transfected cells as endoglycosidase H-sensitive glycoproteins that could form disulfide-bonded homodimers. Cycloheximide-based protein chase experiments showed that the MHC I A-sv1 proteins were more stable than the full-length MHC I A in transiently or stably transfected cell lines. Of particular interest, our studies demonstrated that MHC I A-sv1 could form β2m-free heterodimers with its full-length protein in mammalian cells. The formation of heterodimers was accompanied by a reduction in full-length MHC I A ubiquitination and consequent stabilization of the protein. Taken together, these results demonstrated that MHC I A-sv1 and MHC I A can form a novel heterodimeric complex as a result of the displacement of β2m and illustrated the relevance of regulated MHC I A protein degradation in the β2m-free heterodimerization-dependent control, which may have some implications for the MHC I A splice variant in the fine tuning of classical MHC I A/TCR and MHC I A/killer cell Ig-like receptor interactions.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, People's Republic of China.
authors.forename: Zheng-Xi
authors.initials: ZX
authors.lastname: Dai
authors.forename: Gao-Hong
authors.initials: GH
authors.lastname: Zhang
authors.forename: Xi-He
authors.initials: XH
authors.lastname: Zhang
authors.forename: Hou-Jun
authors.initials: HJ
authors.lastname: Xia
authors.forename: Shao-You
authors.initials: SY
authors.lastname: Li
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D004220:Disulfides / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion / Q000235:genetics / Q000276:immunology; D014162:Transfection; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004220:Disulfides; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D025801:Ubiquitin; D001613:beta 2-Microglobulin