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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Jul 1;172(1):273–283. doi: 10.1084/jem.172.1.273

The role of polymorphic HLA-DR beta chain residues in presentation of viral antigens to T cells

PMCID: PMC2188176  PMID: 2358778

Abstract

The relative importance of 11 polymorphic positions in the HLA-DR7 beta 1 chain in T cell recognition of foreign antigens was investigated using transfectants expressing mutant DR7 beta 1 chains as APC for five rabies virus-specific T cell clones. The results indicate that multiple amino acids, located in both the beta-strands and alpha-helix of DR7 beta 1 in the model of a class II molecule, are involved in DR7- restricted T cell recognition of these antigens. Many of the substitutions appeared to reduce the affinity of an antigenic peptide for the mutant DR7 molecules but did not prevent binding. The heterogeneity of responses of the three G-specific T cell clones to presentation of the G11.3 peptide by several of the mutant DR7 molecules indicates that the T cell receptor (TCR) of each these clones requires a different view of the G11.3/DR7 complex and raises the possibility that the G11.3 peptide may bind to the DR7 molecule in more than one conformation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen P. M., Matsueda G. R., Haber E., Unanue E. R. Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-Ak molecule. J Immunol. 1985 Jul;135(1):368–373. [PubMed] [Google Scholar]
  2. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  3. Barbosa J. A., Santos-Aguado J., Mentzer S. J., Strominger J. L., Burakoff S. J., Biro P. A. Site-directed mutagenesis of class I HLA genes. Role of glycosylation in surface expression and functional recognition. J Exp Med. 1987 Nov 1;166(5):1329–1350. doi: 10.1084/jem.166.5.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhayani H., Paterson Y. Analysis of peptide binding patterns in different major histocompatibility complex/T cell receptor complexes using pigeon cytochrome c-specific T cell hybridomas. Evidence that a single peptide binds major histocompatibility complex in different conformations. J Exp Med. 1989 Nov 1;170(5):1609–1625. doi: 10.1084/jem.170.5.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  6. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  7. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  8. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  9. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [DOI] [PubMed] [Google Scholar]
  10. Cease K. B., Berkower I., York-Jolley J., Berzofsky J. A. T cell clones specific for an amphipathic alpha-helical region of sperm whale myoglobin show differing fine specificities for synthetic peptides. A multiview/single structure interpretation of immunodominance. J Exp Med. 1986 Nov 1;164(5):1779–1784. doi: 10.1084/jem.164.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Celis E., Karr R. W., Dietzschold B., Wunner W. H., Koprowski H. Genetic restriction and fine specificity of human T cell clones reactive with rabies virus. J Immunol. 1988 Oct 15;141(8):2721–2728. [PubMed] [Google Scholar]
  12. Celis E., Ou D., Dietzschold B., Koprowski H. Recognition of rabies and rabies-related viruses by T cells derived from human vaccine recipients. J Virol. 1988 Sep;62(9):3128–3134. doi: 10.1128/jvi.62.9.3128-3134.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davis C. B., Buerstedde J. M., McKean D. J., Jones P. P., McDevitt H. O., Wraith D. C. The role of polymorphic I-Ak beta chain residues in presentation of a peptide from myelin basic protein. J Exp Med. 1989 Jun 1;169(6):2239–2244. doi: 10.1084/jem.169.6.2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davis C. B., Mitchell D. J., Wraith D. C., Todd J. A., Zamvil S. S., McDevitt H. O., Steinman L., Jones P. P. Polymorphic residues on the I-A beta chain modulate the stimulation of T cell clones specific for the N-terminal peptide of the autoantigen myelin basic protein. J Immunol. 1989 Oct 1;143(7):2083–2093. [PubMed] [Google Scholar]
  15. Gregersen P. K., Shen M., Song Q. L., Merryman P., Degar S., Seki T., Maccari J., Goldberg D., Murphy H., Schwenzer J. Molecular diversity of HLA-DR4 haplotypes. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2642–2646. doi: 10.1073/pnas.83.8.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guillet J. G., Lai M. Z., Briner T. J., Smith J. A., Gefter M. L. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature. 1986 Nov 20;324(6094):260–262. doi: 10.1038/324260a0. [DOI] [PubMed] [Google Scholar]
  17. Karr R. W., Gregersen P. K., Obata F., Goldberg D., Maccari J., Alber C., Silver J. Analysis of DR beta and DQ beta chain cDNA clones from a DR7 haplotype. J Immunol. 1986 Nov 1;137(9):2886–2890. [PubMed] [Google Scholar]
  18. Klohe E. P., Watts R., Bahl M., Alber C., Yu W. Y., Anderson R., Silver J., Gregersen P. K., Karr R. W. Analysis of the molecular specificities of anti-class II monoclonal antibodies by using L cell transfectants expressing HLA class II molecules. J Immunol. 1988 Sep 15;141(6):2158–2164. [PubMed] [Google Scholar]
  19. Mellins E., Arp B., Ochs B., Erlich H., Pious D. A single amino acid substitution in the human histocompatibility leukocyte antigen DR3 beta chain selectively alters antigen presentation. J Exp Med. 1988 Nov 1;168(5):1531–1537. doi: 10.1084/jem.168.5.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Norton F. L., Davis C. B., Jones P. P., Goodman J. W. Arsonate-specific murine T cell clones. V. Antigen presentation by L cells transfected with normal and mutant class II genes. J Immunol. 1989 Jul 15;143(2):446–451. [PubMed] [Google Scholar]
  21. Okayama H., Berg P. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol. 1983 Feb;3(2):280–289. doi: 10.1128/mcb.3.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reske-Kunz A. B., Landais D., Peccoud J., Benoist C., Mathis D. Functional sites on the A alpha-chain. Polymorphic residues involved in antigen presentation to insulin-specific, Ab alpha:Ak beta-restricted T cells. J Immunol. 1989 Sep 1;143(5):1472–1481. [PubMed] [Google Scholar]
  23. Ronchese F., Brown M. A., Germain R. N. Structure-function analysis of the Abm12 beta mutation using site-directed mutagenesis and DNA-mediated gene transfer. J Immunol. 1987 Jul 15;139(2):629–638. [PubMed] [Google Scholar]
  24. Schneider L. G., Dietzschold B., Dierks R. E., Matthaeus W., Enzmann P. J., Strohmaier K. Rabies group-specific ribonucleoprotein antigen and a test system for grouping and typing of rhabdoviruses. J Virol. 1973 May;11(5):748–755. doi: 10.1128/jvi.11.5.748-755.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Takebe Y., Seiki M., Fujisawa J., Hoy P., Yokota K., Arai K., Yoshida M., Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. doi: 10.1128/mcb.8.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Taylor J. W., Ott J., Eckstein F. The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNA. Nucleic Acids Res. 1985 Dec 20;13(24):8765–8785. doi: 10.1093/nar/13.24.8765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yu W. Y., Watts R., Karr R. W. Identification of amino acids in HLA-DPw4b beta and -DR5 beta 1 chains that are involved in antibody binding epitopes using site-directed mutagenesis and DNA-mediated gene transfer. Hum Immunol. 1990 Feb;27(2):122–135. doi: 10.1016/0198-8859(90)90109-3. [DOI] [PubMed] [Google Scholar]

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