Home LiteratureArticle Details
PMID: 1836010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire.

The Journal of experimental medicine ·Vol. 174 ·No. 6 ·1991-12-01 ·Pages 1371-83

Casanova JL, Romero P, Widmann C, Kourilsky P, Maryanski JL

Abstract

We report here the first extensive study of a T cell repertoire for a class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) response. We have found that the T cell receptors (TCRs) carried by 28 H-2Kd-restricted CTL clones specific for a single Plasmodium berghei circumsporozoite nonapeptide are highly diverse in terms of V alpha, J alpha, and J beta segments and aminoacid composition of the junctional regions. However, despite this extensive diversity, a high proportion of the TCRs contain the same V beta segment. These results are in contrast to most previously reported T cell responses towards class II MHC-peptide complexes, where the TCR repertoires appeared to be much more limited. In our study, the finding of a dominant V beta in the midst of otherwise highly diverse TCRs suggests the importance of the V beta segment in shaping the T cell repertoire specific for a given MHC-peptide complex. As an additional finding, we observed that nearly all clones have rearranged both TCR alpha loci. Moreover, as many as one-third of the CTL clones that we analyzed apparently display two productive alpha rearrangements. This argues against a regulated model of sequential recombination at the alpha locus and consequently raises the question of whether allelic exclusion of the TCR alpha chain is achieved at all.

MeSH Terms
Alleles Amino Acid Sequence Animals Base Sequence Clone Cells Gene Rearrangement, T-Lymphocyte H-2 Antigens/immunology Mice Mice, Inbred BALB C Molecular Sequence Data Plasmodium berghei/immunology Protozoan Proteins/immunology Receptors, Antigen, T-Cell, alpha-beta/chemistry,genetics T-Lymphocytes, Cytotoxic/immunology Transcription, Genetic
Chemicals
H-2 Antigens Protozoan Proteins Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Casanova J L
Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris.
Romero P
Widmann C
Kourilsky P
Maryanski J L
References (83)
83 references, click to expand
  1. Mechanism and developmental program of immunoglobulin gene rearrangement in mammals.
    Annu Rev Genet. 1989;23:605-36 PMID: 2694945
  2. Synthetic T and B cell recognition sites: implications for vaccine development.
    Adv Immunol. 1989;45:195-282 PMID: 2665439
  3. Implications of a Fab-like structure for the T-cell receptor.
    Immunol Today. 1989 Jan;10(1):10-4 PMID: 2665768
  4. Specificity pockets for the side chains of peptide antigens in HLA-Aw68.
    Nature. 1989 Dec 7;342(6250):692-6 PMID: 2594067
  5. The joining of germ-line V alpha to J alpha genes replaces the preexisting V alpha-J alpha complexes in a T cell receptor alpha, beta positive T cell line.
    Cell. 1988 Oct 21;55(2):291-300 PMID: 3262425
  6. A T cell clone expresses two T cell receptor alpha genes but uses one alpha beta heterodimer for allorecognition and self MHC-restricted antigen recognition.
    Cell. 1988 Oct 7;55(1):49-59 PMID: 3262424
  7. The T cell receptor V alpha 3 gene segment is associated with reactivity to p-azobenzenearsonate.
    Cell. 1988 Jul 15;54(2):247-61 PMID: 3260539
  8. The outline structure of the T-cell alpha beta receptor.
    EMBO J. 1988 Dec 1;7(12):3745-55 PMID: 3208747
  9. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor.
    Nature. 1984 Sep 27-Oct 3;311(5984):344-50 PMID: 6090932
  10. Structure of the human class I histocompatibility antigen, HLA-A2.
    Nature. 1987 Oct 8-14;329(6139):506-12 PMID: 3309677
  11. Dominance of one T-cell receptor in the H-2Kb/TNP response.
    Nature. 1987 Mar 19-25;326(6110):307-9 PMID: 3493439
  12. T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones.
    J Exp Med. 1987 Mar 1;165(3):591-600 PMID: 3493320
  13. Molecular analysis of the antigen receptor of virus-specific cytotoxic T cells and identification of a new V alpha family.
    Eur J Immunol. 1987 Dec;17(12):1843-6 PMID: 2961577
  14. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families.
    Immunol Rev. 1988 Jan;101:149-72 PMID: 2965094
  15. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain.
    Nature. 1985 Aug 29-Sep 4;316(6031):832-6 PMID: 2993908
  16. Preferential expression of a defined T-cell receptor beta-chain gene in hapten-specific cytotoxic T-cell clones.
    Nature. 1986 Jul 24-30;322(6077):376-8 PMID: 3488508
  17. Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes.
    Proc Natl Acad Sci U S A. 1987 Apr;84(7):1992-6 PMID: 3470773
  18. Murine T-cell receptor mutants with deletions of beta-chain variable region genes.
    Proc Natl Acad Sci U S A. 1986 Feb;83(3):767-71 PMID: 3456168
  19. Clonal diversity and T-cell receptor beta-chain variable gene expression in enlarged lymph nodes of MRL-lpr/lpr lupus mice.
    Proc Natl Acad Sci U S A. 1986 Sep;83(18):7018-22 PMID: 3462739
  20. T-cell receptor beta-chain expression: dependence on relatively few variable region genes.
    Science. 1985 Aug 9;229(4713):566-70 PMID: 3875151
  21. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor.
    Nature. 1985 Aug 29-Sep 4;316(6031):783-7 PMID: 3839904
  22. Optimal conditions for directly sequencing double-stranded PCR products with sequenase.
    Nucleic Acids Res. 1990 Jul 11;18(13):4028 PMID: 2374739
  23. On the mechanism of non-allelically excluded V alpha-J alpha T cell receptor secondary rearrangements in a murine T cell lymphoma.
    J Immunol. 1990 Feb 1;144(3):1094-103 PMID: 2153176
  24. Genomic organization of the mouse T cell receptor V alpha family.
    EMBO J. 1990 Jul;9(7):2141-50 PMID: 2357962
  25. The molecular basis of T-cell specificity.
    Annu Rev Immunol. 1990;8:65-82 PMID: 1693083
  26. Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition.
    J Immunol. 1990 Jun 15;144(12):4851-6 PMID: 1693642
  27. Characterization of a rat monoclonal antibody specific for a determinant encoded by the V beta 7 gene segment. Depletion of V beta 7+ T cells in mice with Mls-1a haplotype.
    J Immunol. 1990 May 1;144(9):3473-7 PMID: 1691759
  28. T cell receptor junctional regions and the MHC molecule affect the recognition of antigenic peptides by T cell clones.
    J Immunol. 1990 Feb 1;144(3):1127-35 PMID: 1688589
  29. A novel type of aberrant T cell receptor alpha-chain gene rearrangement. Implications for allelic exclusion and the V-J recombination process.
    J Immunol. 1990 Jun 1;144(11):4410-9 PMID: 2160502
  30. Preferential usage of V alpha 4 and V beta 10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein-specific H-2Db-restricted cytotoxic T cells.
    Eur J Immunol. 1990 Mar;20(3):523-31 PMID: 2138558
  31. Specific deletion of the J-C delta locus in murine alpha/beta T cell clones and studies using transgenic mice.
    Eur J Immunol. 1990 Mar;20(3):517-22 PMID: 2318248
  32. T cell receptor genes in an alloreactive CTL clone: implications for rearrangement and germline diversity of variable gene segments.
    EMBO J. 1986 Sep;5(9):2149-55 PMID: 3490968
  33. Post-transcriptional allelic exclusion of two functionally rearranged T cell receptor alpha genes.
    Int Immunol. 1989;1(3):281-8 PMID: 2562159
  34. Violation of allelic exclusion of the T cell receptor beta genes in a helper T cell clone.
    Int Immunol. 1989;1(3):273-80 PMID: 2562158
  35. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule.
    Nature. 1990 Nov 15;348(6298):213-6 PMID: 1700303
  36. Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin.
    J Exp Med. 1990 Dec 1;172(6):1643-51 PMID: 1701821
  37. H-2Kd-restricted antigenic peptides share a simple binding motif.
    J Exp Med. 1991 Sep 1;174(3):603-12 PMID: 1714934
  38. Isolation and characterization of protective cytolytic T cells in a rodent malaria model system.
    Immunol Lett. 1990 Aug;25(1-3):27-31 PMID: 1704348
  39. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells.
    Nature. 1990 Nov 15;348(6298):252-4 PMID: 1700304
  40. Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus.
    J Virol. 1990 Dec;64(12):5919-26 PMID: 1700830
  41. Each of the two productive T cell receptor alpha-gene rearrangements found in both the A10 and BM 3.3 T cell clones give rise to an alpha chain which can contribute to the constitution of a surface-expressed alpha beta dimer.
    Int Immunol. 1991 Jul;3(7):719-29 PMID: 1655004
  42. Post-translational attainment of allelic exclusion of the T cell receptor alpha chain in a T cell clone.
    Int Immunol. 1991 Jan;3(1):75-82 PMID: 1646625
  43. The T cell antigen receptor: insights into organelle biology.
    Annu Rev Cell Biol. 1990;6:403-31 PMID: 2275818
  44. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention.
    Cell. 1988 Jul 15;54(2):263-73 PMID: 2455603
  45. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy.
    Cell. 1988 Aug 12;54(4):577-92 PMID: 2456857
  46. T cell receptor gene usage in the response to lambda repressor cI protein. An apparent bias in the usage of a V alpha gene element.
    J Exp Med. 1988 Sep 1;168(3):1081-97 PMID: 2971753
  47. Predominant variable region gene usage by gamma/delta T cell receptor-bearing cells in the adult thymus.
    J Exp Med. 1988 Sep 1;168(3):1021-40 PMID: 2971752
  48. The structure of V alpha and J alpha segments in the mouse.
    Nucleic Acids Res. 1988 Dec 9;16(23):11355-64 PMID: 2849763
  49. Selection of amino acid sequences in the beta chain of the T cell antigen receptor.
    Science. 1988 Mar 25;239(4847):1541-4 PMID: 2832942
  50. Expression of two distinct T cell receptor alpha/beta heterodimers by an antigen-specific T cell clone.
    J Exp Med. 1988 Dec 1;168(6):2379-84 PMID: 2848922
  51. Molecular basis for the nonexpression of V beta 17 in some strains of mice.
    J Immunol. 1988 Sep 15;141(6):2165-7 PMID: 2844897
  52. Correlations between T-cell specificity and the structure of the antigen receptor.
    Nature. 1986 May 15-21;321(6067):219-26 PMID: 3012351
  53. Generation of diversity in T cell receptor repertoire specific for pigeon cytochrome c.
    J Exp Med. 1987 Feb 1;165(2):279-301 PMID: 3029266
  54. Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c.
    Nature. 1986 Dec 18-31;324(6098):679-82 PMID: 3025740
  55. Thymocyte circular DNA excised from T cell receptor alpha-delta gene complex.
    EMBO J. 1988 Jun;7(6):1669-74 PMID: 2971535
  56. Highly conserved T-cell receptor junctional regions. Evidence for selection at the protein and the DNA level.
    Immunogenetics. 1990;31(2):118-22 PMID: 2303278
  57. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype.
    J Exp Med. 1984 Aug 1;160(2):452-71 PMID: 6206178
  58. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes.
    Cell. 1981 Dec;27(2 Pt 1):381-90 PMID: 6277505
  59. Localization of a T-cell receptor diversity-region element.
    Nature. 1984 Aug 2-8;310(5976):421-3 PMID: 6611508
  60. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes.
    Nature. 1984 Aug 2-8;310(5976):387-91 PMID: 6336329
  61. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide.
    Cell. 1984 Jul;37(3):1101-10 PMID: 6611207
  62. Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain.
    Cell. 1980 Aug;21(1):1-12 PMID: 6773666
  63. Unusual organization and diversity of T-cell receptor alpha-chain genes.
    Nature. 1985 Aug 29-Sep 4;316(6031):828-32 PMID: 2993907
  64. Variability and repertoire size of T-cell receptor V alpha gene segments.
    Nature. 1985 Oct 3-9;317(6036):430-4 PMID: 2995827
  65. Receptor diversity of insulin-specific T cell lines from C57BL (H-2b) mice.
    J Immunol. 1987 Jun 1;138(11):3991-5 PMID: 2953795
  66. T-cell antigen receptor genes and T-cell recognition.
    Nature. 1988 Aug 4;334(6181):395-402 PMID: 3043226
  67. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria.
    Nature. 1989 Sep 28;341(6240):323-6 PMID: 2477703
  68. Characterization of a naturally processed MHC class II-restricted T-cell determinant of hen egg lysozyme.
    Nature. 1989 Dec 7;342(6250):682-4 PMID: 2480524
  69. T cell receptor gene segment usage in a panel of hen-egg white lysozyme specific, I-Ak-restricted T helper hybridomas.
    J Immunol. 1989 May 1;142(9):3298-304 PMID: 2468715
  70. Site-directed mutations in the VDJ junctional region of a T cell receptor beta chain cause changes in antigenic peptide recognition.
    Cell. 1988 Aug 12;54(4):473-84 PMID: 2456856
  71. Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor.
    Proc Natl Acad Sci U S A. 1988 Oct;85(20):7695-8 PMID: 2459713
  72. Two distinct mechanisms account for the immune response (Ir) gene control of the T cell response to pigeon cytochrome c.
    J Immunol. 1988 Jun 15;140(12):4123-31 PMID: 2453567
  73. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens.
    Nature. 1987 Oct 8-14;329(6139):512-8 PMID: 2443855
  74. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation.
    Nature. 1987 Jun 25-Jul 1;327(6124):677-82 PMID: 2439914
  75. Molecular analysis of antigen recognition by insulin-specific T-cell hybridomas from B6 wild-type and bm12 mutant mice.
    Mol Cell Biol. 1987 May;7(5):1865-72 PMID: 2439899
  76. Immunological self, nonself discrimination.
    Science. 1987 Feb 20;235(4791):865-70 PMID: 2433769
  77. Transfer of specificity by murine alpha and beta T-cell receptor genes.
    Nature. 1986 Mar 20-26;320(6059):232-8 PMID: 2421164
  78. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments.
    Nature. 1985 Aug 8-14;316(6028):517-23 PMID: 2412120
  79. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor.
    J Immunol. 1985 Jun;134(6):3994-4000 PMID: 2580901
  80. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex.
    Annu Rev Immunol. 1985;3:237-61 PMID: 2415139
  81. Derivation of a T cell hybridoma variant deprived of functional T cell receptor alpha and beta chain transcripts reveals a nonfunctional alpha-mRNA of BW5147 origin.
    Eur J Immunol. 1989 Dec;19(12):2269-74 PMID: 2558022
  82. Identification and characterization of new murine T cell receptor beta chain variable region (V beta) genes.
    J Exp Med. 1989 Dec 1;170(6):1987-98 PMID: 2531193
  83. Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells.
    J Exp Med. 1989 Jul 1;170(1):135-43 PMID: 2501444
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1991-12-01
Pages
1371-83
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2119045
Subset
IM
Databases
GENBANK
X60837, X60838, X60839, X60840, X60841, X60842, X60843, X60844, X60845, X60846, X60847, X60848, X60849, X60850, X60851, X60852, X60853, X60854, X60855, X60856, X60857, X60858, X60859, X60860, X60861, X60862, X60863, X60864, X60865, X60866
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com