Home LiteratureArticle Details
PMID: 6189942 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation.

The Journal of experimental medicine ·Vol. 157 ·No. 5 ·1983-05-01 ·Pages 1618-34

Rock KL, Benacerraf B

Abstract

The interaction of nominal Ag with major histocompatibility complex (MHC)-restricted T cells and accessory cells was studied by analyzing the effect of structurally related antigens on the response of antigen-specific MHC-restricted T cell hybridomas. The copolymer L-glutamic acid50-L-tyrosine50 (GT) completely inhibits the response of L-glutamic acid60-L-alanine40-L-tyrosine10 (GAT)-specific, I-Ad-restricted T cell hybridomas to GAT plus accessory cells. This inhibition is specific, as hybridomas of other specificities are not inhibited under identical conditions, and is unique to the GT antigen, as other similar copolymers are not inhibitory. The inhibitory effect is reversible by adding increasing amounts of GAT. Antigen-pulsing experiments localized the inhibition to the level of antigen-presenting cell (APC). GT-prepulsed APC are not inhibitory in cell-mixing experiments and can present other antigens. GT only inhibits the nominal antigen-directed component of a GAT-specific, autoreactive hybrid's response. Together these findings suggest that GT causes inhibition by competing for GAT association at the accessory cell. GT interferes with GAT presentation by an I-Adxb F1 APC to a BALB/c, I-Ad-restricted, but not B10, I-Ab-restricted, T cell hybridoma, and GT inhibits presentation by GAT-prepulsed APC. The implications of these findings for MHC-restricted presentation of antigen are discussed.

MeSH Terms
Animals Binding, Competitive Epitopes Genes, MHC Class II H-2 Antigens/genetics,immunology Hybridomas/immunology Intercellular Signaling Peptides and Proteins Lymphocyte Activation Lymphocyte Cooperation Macromolecular Substances Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Peptides/immunology Polymers Receptors, Antigen, T-Cell/analysis T-Lymphocytes/immunology T-Lymphocytes, Regulatory/immunology
Chemicals
Epitopes H-2 Antigens Intercellular Signaling Peptides and Proteins Macromolecular Substances Peptides Polymers Receptors, Antigen, T-Cell GAT L-glutamic acid-L-tyrosine copolymer
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rock K L
Benacerraf B
References (42)
42 references, click to expand
  1. Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type.
    Science. 1969 Mar 14;163(3872):1207-8 PMID: 5765335
  2. Genetic control of immunological responsiveness in guinea pigs to 2,4-dinitrophenyl conjugates of poly-L-arginine, protamine, and poly-L-ornithine.
    Proc Natl Acad Sci U S A. 1969 Nov;64(3):1095-102 PMID: 4984383
  3. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes.
    J Exp Med. 1973 Nov 1;138(5):1194-212 PMID: 4542806
  4. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response.
    J Exp Med. 1973 Nov 1;138(5):1213-29 PMID: 4126770
  5. The function and interrelationships of T-cell receptors, Ir genes and other histocompatibility gene products.
    Transplant Rev. 1975;22:175-95 PMID: 1078737
  6. Complementation of H-2-linked Ir genes in the mouse.
    Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671-5 PMID: 1059157
  7. Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice.
    J Exp Med. 1975 Dec 1;142(6):1436-46 PMID: 1104746
  8. Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid50-L-tyrosine50 induced in BALB/c mice by cyclophosphamide.
    J Exp Med. 1976 Jul 1;144(1):277-81 PMID: 1084407
  9. Two different VH gene products make up the T-cell receptors.
    Scand J Immunol. 1976;5(9):993-1001 PMID: 63988
  10. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells.
    Nature. 1977 Sep 29;269(5627):417-8 PMID: 302918
  11. The immune response genes of the major histocompatibility complex.
    Immunol Rev. 1978;38:70-119 PMID: 75166
  12. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?
    J Exp Med. 1978 Mar 1;147(3):882-96 PMID: 305459
  13. Cell-mediated immunity and the major histocompatibility complex.
    Rev Physiol Biochem Pharmacol. 1978;81:1-37 PMID: 417392
  14. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes.
    J Immunol. 1978 Jun;120(6):1809-12 PMID: 77879
  15. T cell growth factor: parameters of production and a quantitative microassay for activity.
    J Immunol. 1978 Jun;120(6):2027-32 PMID: 307029
  16. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice.
    Proc Natl Acad Sci U S A. 1978 May;75(5):2439-42 PMID: 307765
  17. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens.
    Curr Top Microbiol Immunol. 1978;81:115-20 PMID: 567555
  18. T-cell inhibition of humoral responsiveness. II. Theory on the role of restrictive recognition in immune regulation.
    Cell Immunol. 1978 Aug;39(1):125-53 PMID: 308845
  19. Two-gene control of the expression of a murine Ia antigen.
    J Exp Med. 1978 Oct 1;148(4):925-39 PMID: 100572
  20. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.
    J Exp Med. 1978 Dec 1;148(6):1510-22 PMID: 102728
  21. Establishment and characterization of BALB/c lymphoma lines with B cell properties.
    J Immunol. 1979 Feb;122(2):549-54 PMID: 310843
  22. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus.
    J Immunol. 1979 Jun;122(6):2491-7 PMID: 87465
  23. Immune response gene control of determinant selection. II. Genetic control of the murine T lymphocyte proliferative response to insulin.
    J Immunol. 1979 Jul;123(1):471-6 PMID: 87482
  24. Determinant selection and macrophage function in genetic control of the immune response.
    Immunol Rev. 1978;40:136-52 PMID: 89077
  25. Interaction between antigen-presenting cells and primed T lymphocytes: an assessment of Ir gene expression in the antigen-presenting cell.
    Immunol Rev. 1978;40:153-80 PMID: 112037
  26. Nature of T lymphocyte recognition of macrophage-associated antigens. II. Macrophage determination of guinea pig T cell responses to human fibrinopeptide B.
    J Immunol. 1979 Sep;123(3):1299-302 PMID: 112188
  27. Monoclonal antibody against an Ir gene product?
    J Exp Med. 1980 Oct 1;152(4):1085-101 PMID: 6158546
  28. 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
  29. 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
  30. A one-receptor view of T-cell behaviour.
    Nature. 1981 Aug 6;292(5823):497-501 PMID: 6166871
  31. Accessory cell stimulation of T cell proliferation requires active antigen processing, Ia-restricted antigen presentation, and a separate nonspecific 2nd signal.
    J Immunol. 1981 Nov;127(5):1964-6 PMID: 6170681
  32. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells.
    Proc Natl Acad Sci U S A. 1982 Jan;79(1):175-8 PMID: 6798568
  33. Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells.
    J Exp Med. 1982 Feb 1;155(2):445-59 PMID: 6460073
  34. Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:E alpha complex expression causes a corresponding defect in antigen-presenting cell function.
    J Exp Med. 1982 Feb 1;155(2):508-23 PMID: 6173457
  35. Antigen presentation by normal B cells, B cell tumors, and macrophages: functional and biochemical comparison.
    J Immunol. 1982 Apr;128(4):1764-8 PMID: 6977567
  36. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation.
    J Exp Med. 1982 Apr 1;155(4):1086-99 PMID: 6174670
  37. The role of Ia molecules in the activation of T lymphocytes. I. The activation of an IL 1-dependent IL 2-producing T cell hybridoma by Con A requires an interaction, which is not H-2-restricted, with an Ia-bearing accessory cell.
    J Immunol. 1982 Oct;129(4):1360-6 PMID: 6809820
  38. Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells.
    J Exp Med. 1982 Sep 1;156(3):918-23 PMID: 6213734
  39. Chemically related antigens compete for presentation by accessory cells to T cells.
    J Immunol. 1982 Nov;129(5):1883-91 PMID: 6181148
  40. The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule.
    J Exp Med. 1983 Jan 1;157(1):359-64 PMID: 6600271
  41. Use of I region-restricted, antigen-specific T cell hybridomas to produce idiotypically specific anti-receptor antibodies.
    J Immunol. 1983 Mar;130(3):1033-7 PMID: 6185566
  42. GENETIC CONTROL IN GUINEA PIGS OF IMMUNE RESPONSE TO CONJUGATES OF HAPTENS AND POLY-L-LYSINE.
    Science. 1965 Jan 29;147(3657):517-8 PMID: 14237210
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.157.5.1618
Published
1983-05-01
Pages
1618-34
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2186997
Subset
IM
Grants
NCI NIH HHS · 2T32-CA-09130-06 · United States
NIAID NIH HHS · AI-14732 · United States
External Links
PubMed source DOI: 10.1084/jem.157.5.1618 PMC Full Text View journal details
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: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2