Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x

The outline structure of the T-cell alpha beta receptor.

C Chothia 1, D R Boswell 1, A M Lesk 1
PMCID: PMC454949  PMID: 3208747

Abstract

From an analysis of the immunoglobulins of known structure we derive a list of 40 sites crucial for the conserved structure of the variable domains. We show that, with marginal exceptions, the sequences of the T-cell alpha beta receptors contain, at sites homologous to these 40, the same or very similar residues. Thus the V alpha-V beta dimer has a framework structure very close to that of the immunoglobulins. Further comparisons show that parts of the surface of the V alpha-V beta framework are hypervariable. They also show that the loops that form the antigen-binding site are similar in size to those commonly found in the immunoglobulins but have different conformations. Only limited sequence variations occur in the first loop of the antigen-binding site in both V alpha and V beta. This, and their geometrical arrangement, suggest that they mainly interact with the MHC proteins.

Full text

PDF
3745

Selected References

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

  1. Alzari P. M., Lascombe M. B., Poljak R. J. Three-dimensional structure of antibodies. Annu Rev Immunol. 1988;6:555–580. doi: 10.1146/annurev.iy.06.040188.003011. [DOI] [PubMed] [Google Scholar]
  2. Amit A. G., Mariuzza R. A., Phillips S. E., Poljak R. J. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science. 1986 Aug 15;233(4765):747–753. doi: 10.1126/science.2426778. [DOI] [PubMed] [Google Scholar]
  3. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  4. Bashford D., Chothia C., Lesk A. M. Determinants of a protein fold. Unique features of the globin amino acid sequences. J Mol Biol. 1987 Jul 5;196(1):199–216. doi: 10.1016/0022-2836(87)90521-3. [DOI] [PubMed] [Google Scholar]
  5. Becker D. M., Pattern P., Chien Y., Yokota T., Eshhar Z., Giedlin M., Gascoigne N. R., Goodnow C., Wolf R., Arai K. Variability and repertoire size of T-cell receptor V alpha gene segments. Nature. 1985 Oct 3;317(6036):430–434. doi: 10.1038/317430a0. [DOI] [PubMed] [Google Scholar]
  6. Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [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. Boswell D. R. A program for template matching of protein sequences. Comput Appl Biosci. 1988 Aug;4(3):345–350. doi: 10.1093/bioinformatics/4.3.345. [DOI] [PubMed] [Google Scholar]
  9. Chien Y., Becker D. M., Lindsten T., Okamura M., Cohen D. I., Davis M. M. A third type of murine T-cell receptor gene. Nature. 1984 Nov 1;312(5989):31–35. doi: 10.1038/312031a0. [DOI] [PubMed] [Google Scholar]
  10. Chothia C., Lesk A. M. Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol. 1987 Aug 20;196(4):901–917. doi: 10.1016/0022-2836(87)90412-8. [DOI] [PubMed] [Google Scholar]
  11. Chothia C., Lesk A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 Apr;5(4):823–826. doi: 10.1002/j.1460-2075.1986.tb04288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chothia C., Novotný J., Bruccoleri R., Karplus M. Domain association in immunoglobulin molecules. The packing of variable domains. J Mol Biol. 1985 Dec 5;186(3):651–663. doi: 10.1016/0022-2836(85)90137-8. [DOI] [PubMed] [Google Scholar]
  13. Concannon P., Pickering L. A., Kung P., Hood L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6598–6602. doi: 10.1073/pnas.83.17.6598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davies D. R., Metzger H. Structural basis of antibody function. Annu Rev Immunol. 1983;1:87–117. doi: 10.1146/annurev.iy.01.040183.000511. [DOI] [PubMed] [Google Scholar]
  15. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  16. Duby A. D., Seidman J. G. Abnormal recombination products result from aberrant DNA rearrangement of the human T-cell antigen receptor beta-chain gene. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4890–4894. doi: 10.1073/pnas.83.13.4890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Epp O., Lattman E. E., Schiffer M., Huber R., Palm W. The molecular structure of a dimer composed of the variable portions of the Bence-Jones protein REI refined at 2.0-A resolution. Biochemistry. 1975 Nov 4;14(22):4943–4952. doi: 10.1021/bi00693a025. [DOI] [PubMed] [Google Scholar]
  18. Furey W., Jr, Wang B. C., Yoo C. S., Sax M. Structure of a novel Bence-Jones protein (Rhe) fragment at 1.6 A resolution. J Mol Biol. 1983 Jul 5;167(3):661–692. doi: 10.1016/s0022-2836(83)80104-1. [DOI] [PubMed] [Google Scholar]
  19. Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
  20. Hochgeschwender U., Simon H. G., Weltzien H. U., Bartels F., Becker A., Epplen J. T. Dominance of one T-cell receptor in the H-2Kb/TNP response. Nature. 1987 Mar 19;326(6110):307–309. doi: 10.1038/326307a0. [DOI] [PubMed] [Google Scholar]
  21. Kievits F., Ivanyi P., Krimpenfort P., Berns A., Ploegh H. L. HLA-restricted recognition of viral antigens in HLA transgenic mice. Nature. 1987 Oct 1;329(6138):447–449. doi: 10.1038/329447a0. [DOI] [PubMed] [Google Scholar]
  22. Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
  23. Klein M. H., Concannon P., Everett M., Kim L. D., Hunkapiller T., Hood L. Diversity and structure of human T-cell receptor alpha-chain variable region genes. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6884–6888. doi: 10.1073/pnas.84.19.6884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  25. Lamoyi E., Angiolillo A. L., Mage R. G. An evolutionary conserved rabbit T-cell receptor beta-chain variable region. Immunogenetics. 1986;23(4):266–270. doi: 10.1007/BF00373022. [DOI] [PubMed] [Google Scholar]
  26. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  27. Leiden J. M., Strominger J. L. Generation of diversity of the beta chain of the human T-lymphocyte receptor for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4456–4460. doi: 10.1073/pnas.83.12.4456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lesk A. M., Chothia C. Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint. Nature. 1988 Sep 8;335(6186):188–190. doi: 10.1038/335188a0. [DOI] [PubMed] [Google Scholar]
  29. Lesk A. M., Chothia C. Evolution of proteins formed by beta-sheets. II. The core of the immunoglobulin domains. J Mol Biol. 1982 Sep 15;160(2):325–342. doi: 10.1016/0022-2836(82)90179-6. [DOI] [PubMed] [Google Scholar]
  30. Lesk A. M., Levitt M., Chothia C. Alignment of the amino acid sequences of distantly related proteins using variable gap penalties. Protein Eng. 1986 Oct-Nov;1(1):77–78. doi: 10.1093/protein/1.1.77. [DOI] [PubMed] [Google Scholar]
  31. Marche P. N., Kindt T. J. Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2190–2194. doi: 10.1073/pnas.83.7.2190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Marquart M., Deisenhofer J., Huber R., Palm W. Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J Mol Biol. 1980 Aug 25;141(4):369–391. doi: 10.1016/0022-2836(80)90252-1. [DOI] [PubMed] [Google Scholar]
  33. Marrack P., Kappler J. The T cell receptor. Science. 1987 Nov 20;238(4830):1073–1079. doi: 10.1126/science.3317824. [DOI] [PubMed] [Google Scholar]
  34. Novotný J., Tonegawa S., Saito H., Kranz D. M., Eisen H. N. Secondary, tertiary, and quaternary structure of T-cell-specific immunoglobulin-like polypeptide chains. Proc Natl Acad Sci U S A. 1986 Feb;83(3):742–746. doi: 10.1073/pnas.83.3.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Patten P., Yokota T., Rothbard J., Chien Y., Arai K., Davis M. M. Structure, expression and divergence of T-cell receptor beta-chain variable regions. Nature. 1984 Nov 1;312(5989):40–46. doi: 10.1038/312040a0. [DOI] [PubMed] [Google Scholar]
  36. Rinaldy A., Wallace R. B., Simon M. M., Becker A., Epplen J. T. A highly homologous T-cell receptor beta-chain variable region is expressed in mouse and human T cells. Immunogenetics. 1985;21(4):403–406. doi: 10.1007/BF00430805. [DOI] [PubMed] [Google Scholar]
  37. Rupp F., Brecher J., Giedlin M. A., Mosmann T., Zinkernagel R. M., Hengartner H., Joho R. H. T-cell antigen receptors with identical variable regions but different diversity and joining region gene segments have distinct specificities but cross-reactive idiotypes. Proc Natl Acad Sci U S A. 1987 Jan;84(1):219–222. doi: 10.1073/pnas.84.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  39. Satow Y., Cohen G. H., Padlan E. A., Davies D. R. Phosphocholine binding immunoglobulin Fab McPC603. An X-ray diffraction study at 2.7 A. J Mol Biol. 1986 Aug 20;190(4):593–604. doi: 10.1016/0022-2836(86)90245-7. [DOI] [PubMed] [Google Scholar]
  40. Saul F. A., Amzel L. M., Poljak R. J. Preliminary refinement and structural analysis of the Fab fragment from human immunoglobulin new at 2.0 A resolution. J Biol Chem. 1978 Jan 25;253(2):585–597. [PubMed] [Google Scholar]
  41. Schiffer M., Wu T. T., Kabat E. A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4461–4463. doi: 10.1073/pnas.83.12.4461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sheriff S., Silverton E. W., Padlan E. A., Cohen G. H., Smith-Gill S. J., Finzel B. C., Davies D. R. Three-dimensional structure of an antibody-antigen complex. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8075–8079. doi: 10.1073/pnas.84.22.8075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Suh S. W., Bhat T. N., Navia M. A., Cohen G. H., Rao D. N., Rudikoff S., Davies D. R. The galactan-binding immunoglobulin Fab J539: an X-ray diffraction study at 2.6-A resolution. Proteins. 1986 Sep;1(1):74–80. doi: 10.1002/prot.340010112. [DOI] [PubMed] [Google Scholar]
  44. Taylor W. R. Identification of protein sequence homology by consensus template alignment. J Mol Biol. 1986 Mar 20;188(2):233–258. doi: 10.1016/0022-2836(86)90308-6. [DOI] [PubMed] [Google Scholar]
  45. Tillinghast J. P., Behlke M. A., Loh D. Y. Structure and diversity of the human T-cell receptor beta-chain variable region genes. Science. 1986 Aug 22;233(4766):879–883. doi: 10.1126/science.3755549. [DOI] [PubMed] [Google Scholar]
  46. Triebel F., Breathnach R., Graziani M., Hercend T., Debre P. Evidence for expression of two distinct T cell receptor beta-chain transcripts in a human diphtheria toxoid-specific T cell clone. J Immunol. 1988 Jan 1;140(1):300–304. [PubMed] [Google Scholar]
  47. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  48. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]
  50. Yoshikai Y., Kimura N., Toyonaga B., Mak T. W. Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes. J Exp Med. 1986 Jul 1;164(1):90–103. doi: 10.1084/jem.164.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES