Inhibition of Antigen-specific T Lymphocyte Activation by Structurally Related Ir Gene-controlled Polymers. II. Competitive Inhibition of I-E-restricted, Antigen-specific T Cell Responses

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1984 Dec 1

PMID 6210339

Citations 7

Authors

K L Rock

B Benacerraf

Affiliations

Soon will be listed here.

Abstract

Our previous studies have defined a highly specific competitive inhibition between a pair of structurally related antigens (GT and GAT) for antigen presentation by accessory cells. The present report investigates this phenomenon in a second antigenic system, which is controlled by a distinct Ir gene product. Two GL phi-specific, I-Ed-restricted, interleukin 2-producing T cell hybridomas were constructed. The antigenic fine specificity of these two hybrid clones was distinct. One hybrid reacted solely with GL phi while the second cross-reacted with GLleu and GLT. These latter two copolymers, as well as the antigen GL, were found to inhibit the GL phi response of the non-cross-reactive hybrid. The structurally related antigen G phi was not inhibitory for this clone's response. The cross-reactive GL phi hybrid could also be inhibited, but, in this case, G phi and not GL caused the inhibition. Reciprocal inhibitions could be demonstrated between these and other hybrids (e.g., GAT responsive), indicating a very high degree of specificity to the inhibition. The inhibition caused by the various copolymers was reversible by increasing the concentration of GL phi, This effect was localized to the antigen-presenting cell and not the T cell hybridoma. Functionally, this competition did not appear to be for antigen uptake or general antigen processing. These findings generalize the phenomenon of antigen competition to a second antigen system in the context of a second Ia molecule. The possible mechanisms accounting for the complex pattern of specificities in this system are discussed.

Citing Articles

Significance and biological function of class II MHC molecules. Rous-Whipple Award lecture 1985.

Benacerraf B Am J Pathol. 1985; 120(3):334-43.

PMID: 3929612 PMC: 1887982.

Phospholipase treatment of accessory cells that have been exposed to antigen selectively inhibits antigen-specific Ia-restricted, but not allospecific, stimulation of T lymphocytes.

Falo Jr L, Benacerraf B, Rock K Proc Natl Acad Sci U S A. 1986; 83(18):6994-7.

PMID: 3529095 PMC: 386638. DOI: 10.1073/pnas.83.18.6994.

Characterization of antigen association with accessory cells: specific removal of processed antigens from the cell surface by phospholipases.

Falo Jr L, Haber S, Herrmann S, Benacerraf B, Rock K Proc Natl Acad Sci U S A. 1987; 84(2):522-6.

PMID: 3467371 PMC: 304241. DOI: 10.1073/pnas.84.2.522.

Antigenic competition at the level of peptide-Ia binding.

Babbitt B, Matsueda G, Haber E, UNANUE E, Allen P Proc Natl Acad Sci U S A. 1986; 83(12):4509-13.

PMID: 3459185 PMC: 323763. DOI: 10.1073/pnas.83.12.4509.

Virus-immune T cells and the major histocompatibility complex: evolution of some basic concepts over the past two years.

Doherty P Experientia. 1986; 42(9):972-7.

PMID: 3093266 DOI: 10.1007/BF01940699.

References

Rosenthal A, Shevach E . Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973; 138(5):1194-212. PMC: 2139433. DOI: 10.1084/jem.138.5.1194. View

Rock K, Benacerraf B . 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; 157(1):359-64. PMC: 2186913. DOI: 10.1084/jem.157.1.359. View

Dorf M, Benacerraf B . Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975; 72(9):3671-5. PMC: 433058. DOI: 10.1073/pnas.72.9.3671. View

Dorf M, Maurer P, Merryman F, Benacerraf B . Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes. J Exp Med. 1976; 143(4):889-96. PMC: 2190170. DOI: 10.1084/jem.143.4.889. View

Dorf M, Twigg M, Benacerraf B . Genetic control of the immune response to the radom linear terpolymer of L-glutamic acid, L-lysine and L-leucine (GLleu) by complementing Ir genes. Eur J Immunol. 1976; 6(8):552-6. DOI: 10.1002/eji.1830060805. View

Benacerraf B, Germain R . The immune response genes of the major histocompatibility complex. Immunol Rev. 1978; 38:70-119. DOI: 10.1111/j.1600-065x.1978.tb00385.x. View

Benacerraf B . 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; 120(6):1809-12. View

Kim K, Kanellopoulos-Langevin C, MERWIN R, Sachs D, Asofsky R . Establishment and characterization of BALB/c lymphoma lines with B cell properties. J Immunol. 1979; 122(2):549-54. View

Rosenthal A . Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978; 40:136-52. DOI: 10.1111/j.1600-065x.1978.tb00404.x. View

10.

Schwartz R, Yano A, Paul W . 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. DOI: 10.1111/j.1600-065x.1978.tb00405.x. View

11.

Ozato K, Mayer N, Sachs D . Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980; 124(2):533-40. View

12.

Rock K, Benacerraf B . Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation. J Exp Med. 1983; 157(5):1618-34. PMC: 2186997. DOI: 10.1084/jem.157.5.1618. View

13.

Shimonkevitz R, Kappler J, Marrack P, Grey H . Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983; 158(2):303-16. PMC: 2187345. DOI: 10.1084/jem.158.2.303. View

14.

Marrack P, Shimonkevitz R, Hannum C, Haskins K, Kappler J . The major histocompatibility complex-restricted antigen receptor on T cells. IV. An antiidiotypic antibody predicts both antigen and I-specificity. J Exp Med. 1983; 158(5):1635-46. PMC: 2187134. DOI: 10.1084/jem.158.5.1635. View

15.

Rock K, Benacerraf B . MHC-restricted T cell activation: analysis with T cell hybridomas. Immunol Rev. 1983; 76:29-57. DOI: 10.1111/j.1600-065x.1983.tb01096.x. View

16.

Rock K, Benacerraf B . Selective modification of a private I-A allo-stimulating determinant(s) upon association of antigen with an antigen-presenting cell. J Exp Med. 1984; 159(4):1238-52. PMC: 2187280. DOI: 10.1084/jem.159.4.1238. View

17.

Heber-Katz E, Hansburg D, Schwartz R . The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation. J Mol Cell Immunol. 1983; 1(1):3-18. View

18.

Kappler J, Skidmore B, White J, Marrack P . Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981; 153(5):1198-214. PMC: 2186156. DOI: 10.1084/jem.153.5.1198. View

19.

Werdelin O . Chemically related antigens compete for presentation by accessory cells to T cells. J Immunol. 1982; 129(5):1883-91. View

20.

Rock K, Barnes M, Germain R, Benacerraf B . The role of Ia molecules in the activation of T lymphocytes. II. Ia-restricted recognition of allo K/D antigens is required for class I MHC-stimulated mixed lymphocyte responses. J Immunol. 1983; 130(1):457-62. View