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. 1987 Feb;84(4):1090–1093. doi: 10.1073/pnas.84.4.1090

A single base mutation in an I-A alpha-chain gene alters T-cell recognition.

I J Griffith, E M Choi, L H Glimcher
PMCID: PMC304367  PMID: 3493486

Abstract

The interaction between the clonally selected T-cell antigen receptor, antigen, and Ia molecule is poorly understood at the molecular level. A cell line bearing an altered I-Ak alpha-chain (Ak alpha) molecule has been examined in order to provide more information about the relationship between Ia structure and function. The cell line, 3J9, was derived from the TA3 B-cell hybridoma through a series of negative and positive immunoselection steps. The 3J9 mutant lacked the binding site recognized by the Ak alpha-specific monoclonal antibody 39J and failed to present antigen to two T-cell hybridomas out of a large panel of I-Ak-restricted T-cell hybridomas examined. Sequence analysis of the mutant Ak alpha gene showed a single base transition (G----A) that resulted in a glutamic acid to lysine substitution at amino acid 75 of the alpha 1 domain. This mutation confirms the importance of amino acid 75 in the expression of the Ia.19 epitope, demonstrates the involvement of this region in the presentation of antigen to specific T cells, and provides a further example of the multiple functional domains on the Ia molecule that are involved in antigen presentation.

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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., McKean D. J., Beck B. N., Sheffield J., Glimcher L. H. Direct evidence that a class II molecule and a simple globular protein generate multiple determinants. J Exp Med. 1985 Oct 1;162(4):1264–1274. doi: 10.1084/jem.162.4.1264. [DOI] [PMC free article] [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. Beck B. N., Buerstedde J. M., Krco C. J., Nilson A. E., Chase C. G., McKean D. J. Characterization of cell lines expressing mutant I-Ab and I-Ak molecules allows the definition of distinct serologic epitopes on A alpha and A beta polypeptides. J Immunol. 1986 Apr 15;136(8):2953–2961. [PubMed] [Google Scholar]
  4. Beck B. N., Glimcher L. H., Nilson A. E., Pierres M., McKean D. J. The structure-function relationship of I-A molecules: correlation of serologic and functional phenotypes of four I-Ak mutant cell lines. J Immunol. 1984 Dec;133(6):3176–3182. [PubMed] [Google Scholar]
  5. Ben-Nun A., Choi E., McIntyre K. R., Leeman S. A., McKean D. J., Seidman J. G., Glimcher L. H. DNA-mediated transfer of major histocompatibility class II I-Ab and I-Abm12 genes into B lymphoma cells: molecular and functional analysis of introduced antigens. J Immunol. 1985 Aug;135(2):1456–1464. [PubMed] [Google Scholar]
  6. Benacerraf B., Germain R. N. The immune response genes of the major histocompatibility complex. Immunol Rev. 1978;38:70–119. doi: 10.1111/j.1600-065x.1978.tb00385.x. [DOI] [PubMed] [Google Scholar]
  7. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. Regions of allelic hypervariability in the murine A alpha immune response gene. Cell. 1983 Aug;34(1):169–177. doi: 10.1016/0092-8674(83)90147-2. [DOI] [PubMed] [Google Scholar]
  8. Brown M. A., Glimcher L. A., Nielsen E. A., Paul W. E., Germain R. N. T-cell recognition of Ia molecules selectively altered by a single amino acid substitution. Science. 1986 Jan 17;231(4735):255–258. doi: 10.1126/science.3484558. [DOI] [PubMed] [Google Scholar]
  9. Cohn L. E., Glimcher L. H., Waldmann R. A., Smith J. A., Ben-Nun A., Seidman J. G., Choi E. Identification of functional regions on the I-Ab molecule by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1986 Feb;83(3):747–751. doi: 10.1073/pnas.83.3.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cullen S. E., Freed J. H., Nathenson S. G. Structural and serological properties of murine Ia alloantigens. Transplant Rev. 1976;30:236–270. doi: 10.1111/j.1600-065x.1976.tb00222.x. [DOI] [PubMed] [Google Scholar]
  11. Glimcher L. H., Hamano T., Asofsky R., Herber-Katz E., Hedrick S., Schwartz R. H., Paul W. E. I region-restricted antigen presentation by B cell-B lymphoma hybridomas. Nature. 1982 Jul 15;298(5871):283–284. doi: 10.1038/298283a0. [DOI] [PubMed] [Google Scholar]
  12. Glimcher L. H., Hamano T., Asofsky R., Sachs D. H., Pierres M., Samelson L. E., Sharrow S. O., Paul W. E. IA mutant functional antigen-presenting cell lines. J Immunol. 1983 May;130(5):2287–2294. [PubMed] [Google Scholar]
  13. Glimcher L. H., Sharrow S. O., Paul W. E. Serologic and functional characterization of a panel of antigen-presenting cell lines expressing mutant I-A class II molecules. J Exp Med. 1983 Nov 1;158(5):1573–1588. doi: 10.1084/jem.158.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KRIEG D. R. Ethyl methanesulfonate-induced reversion of bacteriophage T4rII mutants. Genetics. 1963 Apr;48:561–580. doi: 10.1093/genetics/48.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Landais D., Matthes H., Benoist C., Mathis D. A molecular basis for the Ia.2 and Ia.19 antigenic determinants. Proc Natl Acad Sci U S A. 1985 May;82(9):2930–2934. doi: 10.1073/pnas.82.9.2930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mathis D. J., Benoist C. O., Williams V. E., 2nd, Kanter M. R., McDevitt H. O. The murine E alpha immune response gene. Cell. 1983 Mar;32(3):745–754. doi: 10.1016/0092-8674(83)90060-0. [DOI] [PubMed] [Google Scholar]
  17. McIntyre K. R., Seidman J. G. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature. 1984 Apr 5;308(5959):551–553. doi: 10.1038/308551a0. [DOI] [PubMed] [Google Scholar]
  18. Nairn R., Yamaga K., Nathenson S. G. Biochemistry of the gene products from murine MHC mutants. Annu Rev Genet. 1980;14:241–277. doi: 10.1146/annurev.ge.14.120180.001325. [DOI] [PubMed] [Google Scholar]
  19. Norcross M. A., Bentley D. M., Margulies D. H., Germain R. N. 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):1316–1337. doi: 10.1084/jem.160.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pierres M., Devaux C., Dosseto M., Marchetto S. 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):481–495. doi: 10.1007/BF00350120. [DOI] [PubMed] [Google Scholar]
  21. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  22. Schlauder G. G., Bell M. P., Beck B. N., Nilson A., McKean D. J. The structure-function relationship of I-A molecules: a biochemical analysis of I-A polypeptides from mutant antigen-presenting cells and evidence of preferential association of allelic forms. J Immunol. 1985 Sep;135(3):1945–1954. [PubMed] [Google Scholar]
  23. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]

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