Abstract

The specific aims of this proposal are as follows: 1) To construct a cDNA library from the mRNAs of a number of homozygous lymphoblastoid cell lines and clone full-length cDNA copies in E. coli, to sequence the cDNA inserts and from them deduce the amino acid sequences of a number of HLA-A, -B, and -C antigen alleles; 2) To isolate genomic clones from human genomic libraries established from homozygous lymphoblastoid cell lines and to analyze these genomic clones and their flanking regions, to study expression of the genomic clones in several systems with a view to using this technique in identification of the clones; 3) To attempt to obtain cDNA clones corresponding to the heavy and light chains of HLA-DR antigens and of the human equivalent of the murine TL and Qa antigens; 4) To study at the genetic level the relationship between a number of human diseases and particular antigens in the HLA region, particularly ankylosing spondylitis (HLA-B27, hereditary hemochromatosis (HLA-A3), multiple sclerosis (HLA-DR), juvenile onset diabetes (HLA-DR3 and 4) and rheumatoid arthritis (HLA-DR4).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK030241-08
Application #
3483542
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1982-01-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Sugawara, M; Scholl, T; Mahanta, S K et al. (1995) Cooperativity between the J and S elements of class II major histocompatibility complex genes as enhancers in normal and class II-negative patient and mutant B cell lines. J Exp Med 182:175-84
Cella, M; Longo, A; Ferrara, G B et al. (1994) NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80. J Exp Med 180:1235-42
Colonna, M; Borsellino, G; Falco, M et al. (1993) HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. Proc Natl Acad Sci U S A 90:12000-4
Ponath, P D; Fass, D; Liou, H C et al. (1993) The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes. J Biol Chem 268:17074-82
Sugawara, M; Ponath, P D; Yang, Z et al. (1992) Interferon-gamma response region in the promoter of the class II MHC gene, DPA. Hum Immunol 35:157-64
Fabbi, M; Groh, V; Strominger, J L (1992) IL-7 induces proliferation of CD3-/low CD4- CD8- human thymocyte precursors by an IL-2 independent pathway. Int Immunol 4:1-5
Colonna, M; Bresnahan, M; Bahram, S et al. (1992) Allelic variants of the human putative peptide transporter involved in antigen processing. Proc Natl Acad Sci U S A 89:3932-6
Colonna, M; Spies, T; Strominger, J L et al. (1992) Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. Proc Natl Acad Sci U S A 89:7983-5
Ono, S J; Bazil, V; Sugawara, M et al. (1991) An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP. J Exp Med 173:629-37
Ono, S J; Bazil, V; Levi, B Z et al. (1991) Transcription of a subset of human class II major histocompatibility complex genes is regulated by a nucleoprotein complex that contains c-fos or an antigenically related protein. Proc Natl Acad Sci U S A 88:4304-8

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