HLA-DMA AND HLA-DMB GENES ARE BOTH REQUIRED FOR MHC CLASS-II PEPTIDE COMPLEX-FORMATION IN ANTIGEN-PRESENTING CELLS

被引:281
|
作者
FLING, SP
ARP, B
PIOUS, D
机构
[1] UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195
[2] UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195
[3] UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195
关键词
D O I
10.1038/368554a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MAJOR histocompatibility complex (MHC) class II molecules are highly polymorphic cell-surface glycoproteins that present antigenic peptides to CD4+ T lymphocytes. The normal assembly of class II molecules with cognate peptides for antigen presentation requires an accessory function provided by a gene mapping to the class II region of the HLA complex1,2. The isolation of somatic cell mutants of antigen-presenting cells (APC) has shown that at least one gene which maps between HLA-DP and HLA-DQ, provisionally designated c2p-1 (ref. 3), mediates this process1,2,4. Here we describe a unique new mutant 2.2.93, which manifests defective formation of class II/peptide complexes like that described in c2p-1 mutants. We show that (1) mutant 2.2.93 contains a mutation in HLA-DMA5, and a representative c2p-1 mutant, 9.5.3, contains a mutation in HLA-DMB5; and (2) transfection and expression of DMA complementary DNA in 2.2.93, and DMB cDNA in 9.5.3, reverses their mutant phenotypes. These results show that HLA-DMA and -DMB, genes of previously unknown function mapping between HLA-DP and HLA-DQ5, are required for the normal assembly of peptides with MHC class II molecules. They suggest that HLA-DMA and -DMB encode subunits of a functional heterodimer which is critical in the pathway of class II antigen presentation.
引用
收藏
页码:554 / 558
页数:5
相关论文
共 50 条
  • [41] MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-II ANTIGEN (HLA-DR, DQ, AND DP) EXPRESSION IN HUMAN-FETAL ENDOCRINE ORGANS AND GUT
    OLIVER, AM
    THOMSON, AW
    SEWELL, HF
    ABRAMOVICH, DR
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1988, 27 (06) : 731 - 737
  • [42] MHC class II-presented peptide repertoires derived from human antigen-presenting cells pulsed with blood coagulation factor VIII
    van Haren, S. D.
    Herczenik, E.
    ten Brinke, A.
    Mertens, K.
    Meijer, A.
    Voorberg, J.
    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 : 269 - 269
  • [43] DOWN-REGULATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ON ANTIGEN-PRESENTING CELLS AFTER INTERACTION WITH HELPER T-CELLS
    VIDOVIC, D
    FALCIONI, F
    BOLIN, DR
    NAGY, ZA
    EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (05) : 1326 - 1331
  • [44] MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN (HLA-DR) EXPRESSION BY ILEAL EPITHELIAL-CELLS IN PATIENTS WITH SERONEGATIVE SPONDYLARTHROPATHY
    CUVELIER, C
    MIELANTS, H
    DEVOS, M
    VEYS, E
    ROELS, H
    GUT, 1990, 31 (05) : 545 - 549
  • [45] Artificial antigen-presenting cells expressing HLA class II molecules as an effective tool for amplifying human specific memory CD4+ T cells
    Garnier, Anthony
    Hamieh, Mohamad
    Drouet, Aurelie
    Leprince, Jerome
    Vivien, Denis
    Frebourg, Thierry
    Le Mauff, Brigitte
    Latouche, Jean-Baptiste
    Toutirais, Olivier
    IMMUNOLOGY AND CELL BIOLOGY, 2016, 94 (07): : 662 - 672
  • [46] HUMAN OSTEOBLAST-LIKE CELLS EXPRESSING MHC CLASS-II DETERMINANTS STIMULATE ALLOGENEIC AND AUTOLOGOUS PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND FUNCTION AS ANTIGEN-PRESENTING CELLS
    SKJODT, H
    MOLLER, T
    FREIESLEBEN, SF
    IMMUNOLOGY, 1989, 68 (03) : 416 - 420
  • [47] PRESENTATION OF THE PLASMODIUM-FALCIPARUM ANTIGEN PF155/RESA TO HUMAN T-CELLS - VARIATIONS IN RESPONSIVENESS INDUCED BY ANTIGEN-PRESENTING CELLS FROM DIFFERENT BUT MHC CLASS-II IDENTICAL DONORS
    TROYEBLOMBERG, M
    LEPERS, JP
    SJOBERG, K
    RAHALIMALALA, L
    LARSSON, A
    OLERUP, O
    PERLMANN, P
    IMMUNOLOGY LETTERS, 1994, 43 (1-2) : 59 - 66
  • [48] IN CUTANEOUS T-CELL LYMPHOMA, CLASS-II MHC MOLECULES ON CD1(+) ANTIGEN-PRESENTING CELLS ARE UP-REGULATED IN INVOLVED COMPARED WITH UNINVOLVED EPIDERMIS
    HANSEN, ER
    BANG, B
    LARSEN, JK
    VEJLSGAARD, GL
    BAADSGAARD, O
    BRITISH JOURNAL OF DERMATOLOGY, 1994, 131 (06) : 780 - 788
  • [49] SYNTHETIC COPOLYMER-1 INHIBITS THE BINDING OF MBP, PLP AND MOG PEPTIDES TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ON ANTIGEN-PRESENTING CELLS
    FRIDKISHARELI, M
    TEITELBAUM, D
    DEROSBO, NK
    AMON, R
    SELA, M
    JOURNAL OF NEUROCHEMISTRY, 1994, 63 : S61 - S61
  • [50] IDENTIFICATION OF TRANSCRIPTS OF THE T-CELL ANTIGEN RECEPTOR BETA-CHAIN GENE AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES IN ANTIGEN-PRESENTING CLONED BK-BI-2.6.C6 CELLS
    RESKEKUNZ, AB
    RUCK, G
    STEINLEIN, P
    RESKE, K
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1988, 27 (01) : 107 - 112