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PMID: 3921966 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

"Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.

Germain RN, Ashwell JD, Lechler RI, Margulies DH, Nickerson KM, Suzuki G, Tou JY

Abstract

To investigate the role of the highly polymorphic amino-terminal (beta 1) domain of the class II major histocompatibility polypeptide A beta during recognition by T cells and antibodies, "exon-shuffling" was carried out between genomic recombinant DNA clones of Ak beta and Ad beta to generate a hybrid gene containing Ak beta exons for the amino-terminal domain followed by the Ad beta exons for the remainder of the molecule. L-cell gene transfectants expressing this hybrid A beta gene in combination with Ak alpha were compared to L cells expressing wild-type Ak beta Ak alpha dimers in tests of antigen-presentation to T-cell clones and hybridomas and for staining by a panel of anti-I-Ak-specific monoclonal antibodies. These antibodies were also tested for their reactivity with a B-lymphoma transfectant expressing Ak beta in the absence of Ak alpha. The results showed no qualitative differences in either T-cell or antibody-mediated recognition of I-Ak molecules containing either the exon-shuffled or wildtype Ak beta. Together with the data involving the B cell transfectant expressing only Ak beta, these results map control of the A beta contribution to the immunologically relevant determinants of I-Ak to the highly polymorphic amino-terminal domain and indicate little, if any, contribution to allele-specific recognition by amino acid sequence variations in the remaining portions of the A beta polypeptide.

MeSH Terms
Alleles Animals Base Sequence Binding Sites DNA, Recombinant Genes, MHC Class II Histocompatibility Antigens Class II/genetics,immunology Isoantibodies/immunology L Cells/immunology Mice T-Lymphocytes/immunology
Chemicals
DNA, Recombinant Histocompatibility Antigens Class II Isoantibodies
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Germain R N
Ashwell J D
Lechler R I
Margulies D H
Nickerson K M
Suzuki G
Tou J Y
References (42)
42 references, click to expand
  1. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition.
    J Exp Med. 1981 May 1;153(5):1198-214 PMID: 6166712
  2. Selective loss of antigen-specific Ir gene function in IA mutant B6.C-H-2bm12 is an antigen presenting cell defect.
    Proc Natl Acad Sci U S A. 1981 Oct;78(10):6406-10 PMID: 7031650
  3. Clonal analysis of B- and T-cell responses to Ia antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies.
    Immunogenetics. 1981 Dec;14(6):481-95 PMID: 6976317
  4. Establishment of B cell hybridomas with B cell surface antigens.
    J Immunol. 1982 Oct;129(4):1403-6 PMID: 6809823
  5. A molecular map of the immune response region from the major histocompatibility complex of the mouse.
    Nature. 1982 Nov 4;300(5887):35-42 PMID: 6290895
  6. Monoclonal antibodies to mouse major histocompatibility complex antigens.
    Transplantation. 1982 Sep;34(3):113-20 PMID: 7135466
  7. Expression of H-2Dd and H-2Ld mouse major histocompatibility antigen genes in L cells after DNA-mediated gene transfer.
    J Immunol. 1983 Jan;130(1):463-70 PMID: 6571712
  8. DNA sequence of the gene encoding the E alpha Ia polypeptide of the BALB/c mouse.
    Science. 1982 Dec 17;218(4578):1229-32 PMID: 6815800
  9. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens.
    Nature. 1982 Dec 23;300(5894):755-7 PMID: 6184620
  10. The murine E alpha immune response gene.
    Cell. 1983 Mar;32(3):745-54 PMID: 6403249
  11. Clonal analysis of the major histocompatibility complex restriction and the fine specificity of antigen recognition in the T cell proliferative response to cytochrome C.
    J Immunol. 1983 Apr;130(4):1527-35 PMID: 6187812
  12. IA mutant functional antigen-presenting cell lines.
    J Immunol. 1983 May;130(5):2287-94 PMID: 6300242
  13. Use of DNA-mediated gene transfer to analyze the role of H-2Ld in controlling the specificity of anti-vesicular stomatitis virus cytotoxic T cells.
    J Exp Med. 1983 Apr 1;157(4):1261-72 PMID: 6187888
  14. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells.
    Mol Cell Biol. 1983 Feb;3(2):280-9 PMID: 6300662
  15. Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or C1 domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer.
    Proc Natl Acad Sci U S A. 1983 May;80(9):2709-12 PMID: 6302702
  16. Murine I-A beta chain polymorphism: nucleotide sequences of three allelic I-A beta genes.
    Science. 1983 Jul 15;221(4607):283-6 PMID: 6407114
  17. Nucleotide sequence of a light chain gene of the mouse I-A subregion: A beta d.
    Science. 1983 Aug 19;221(4612):750-4 PMID: 6410508
  18. Regions of allelic hypervariability in the murine A alpha immune response gene.
    Cell. 1983 Aug;34(1):169-77 PMID: 6309407
  19. Structure of the murine immune response I-A beta locus: sequence of the I-A beta gene and an adjacent beta-chain second domain exon.
    Cell. 1983 Aug;34(1):179-88 PMID: 6411350
  20. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520-4 PMID: 6310581
  21. Extensive polymorphism surrounding the murine Ia A beta chain gene.
    J Immunol. 1983 Oct;131(4):2025-31 PMID: 6311906
  22. Functional expression of a transfected murine class II MHC gene.
    Nature. 1983 Nov 10-16;306(5939):190-4 PMID: 6606131
  23. Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines.
    Cell. 1984 Feb;36(2):319-27 PMID: 6607120
  24. Multiple functional sites on a single Ia molecule defined using T cell clones and antibodies with chain-determined specificity.
    J Exp Med. 1984 Mar 1;159(3):704-15 PMID: 6421980
  25. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes.
    Nature. 1984 Apr 5-11;308(5959):551-3 PMID: 6324001
  26. Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain.
    Proc Natl Acad Sci U S A. 1983 Dec;80(24):7621-5 PMID: 6324181
  27. Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains.
    EMBO J. 1984 Feb;3(2):447-52 PMID: 6585297
  28. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens.
    Curr Top Microbiol Immunol. 1978;81:115-20 PMID: 567555
  29. B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse.
    J Exp Med. 1979 Dec 1;150(6):1323-38 PMID: 159937
  30. Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice.
    Immunol Rev. 1979;47:175-206 PMID: 398326
  31. Distinct epitopes of Ik gene products identified by monoclonal antibodies.
    Eur J Immunol. 1980 Dec;10(12):950-7 PMID: 6162651
  32. Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation.
    Proc Natl Acad Sci U S A. 1981 Mar;78(3):1853-7 PMID: 6165020
  33. Ir gene function in an I-A subregion mutant B6.C-H-2bm12.
    J Exp Med. 1981 Feb 1;153(2):464-9 PMID: 6787167
  34. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072-6 PMID: 7017722
  35. Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites.
    Nature. 1984 May 17-23;309(5965):279-81 PMID: 6201750
  36. Cell-type-specific cDNA probes and the murine I region: the localization and orientation of Ad alpha.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):2194-8 PMID: 6326111
  37. Dissection of serological and cytolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains.
    J Exp Med. 1984 Jul 1;160(1):167-78 PMID: 6203998
  38. The nucleotide sequence of the murine I-E beta b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex.
    EMBO J. 1984 Jun;3(6):1221-5 PMID: 6086309
  39. Cytolytic T cells recognize the two amino-terminal domains of H-2 K antigens in tandem in influenza A infected cells.
    Cell. 1984 Aug;38(1):79-87 PMID: 6088078
  40. Membrane Ia expression and antigen-presenting accessory cell function of L cells transfected with class II major histocompatibility complex genes.
    J Exp Med. 1984 Nov 1;160(5):1316-37 PMID: 6436430
  41. Genes of the major histocompatibility complex of the mouse.
    Annu Rev Immunol. 1983;1:529-68 PMID: 6152713
  42. Molecular characterization of the recombination region of six murine major histocompatibility complex (MHC) I-region recombinants.
    J Mol Cell Immunol. 1984;1(2):125-35 PMID: 6152893
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1985-05-00
Pages
2940-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC397682
Subset
IM
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