Thymus-leukemia antigen interacts with T cells and self-peptides

Padmanee Sharma, Sebastian Joyce, Karen A. Chorney, James W. Griffith, Robert H. Bonneau, Frank D. Wilson, Colena A. Johnson, Richard A. Flavell, Michael J. Chorney

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18(d) gene product on essentially all nucleated cells through the control of a heterologous H-2Kb gene promoter. Transgenic mice demonstrated an increase in the number of CD4+ lymphocytes within the thymus and lymph nodes; these cells displayed an altered T cell receptor repertoire possibly suggesting a role for the ectopically expressed TL protein. The TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid and vigorous immunologic rejection of the allograft. In MLR studies, transgenic stimulator cells induced the proliferation of responders to a level intermediate between genetically identical and H-2-disparate responder-stimulator combinations. The TL protein was also capable of stimulating cytotoxic T lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further data demonstrated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell surface. Together, these data suggest that H-2T18(d) is capable of interacting with T cells via a bound peptide. These data further support the possibility that TL may subserve a specialized function within the immunologic system.

Original languageEnglish (US)
Pages (from-to)987-996
Number of pages10
JournalJournal of Immunology
Volume156
Issue number3
StatePublished - Feb 1 1996

Fingerprint

Thymus Gland
Leukemia
T-Lymphocytes
Peptides
Transgenic Mice
Proteins
thymus-leukemia antigens
Genetically Modified Animals
Histocompatibility
Lymphocyte Count
Cytotoxic T-Lymphocytes
Intestinal Mucosa
T-Cell Antigen Receptor
Genes
Allografts
Transplantation
Lymph Nodes
Cell Proliferation
Transplants
Skin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Sharma, P., Joyce, S., Chorney, K. A., Griffith, J. W., Bonneau, R. H., Wilson, F. D., ... Chorney, M. J. (1996). Thymus-leukemia antigen interacts with T cells and self-peptides. Journal of Immunology, 156(3), 987-996.
Sharma, Padmanee ; Joyce, Sebastian ; Chorney, Karen A. ; Griffith, James W. ; Bonneau, Robert H. ; Wilson, Frank D. ; Johnson, Colena A. ; Flavell, Richard A. ; Chorney, Michael J. / Thymus-leukemia antigen interacts with T cells and self-peptides. In: Journal of Immunology. 1996 ; Vol. 156, No. 3. pp. 987-996.
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abstract = "The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18(d) gene product on essentially all nucleated cells through the control of a heterologous H-2Kb gene promoter. Transgenic mice demonstrated an increase in the number of CD4+ lymphocytes within the thymus and lymph nodes; these cells displayed an altered T cell receptor repertoire possibly suggesting a role for the ectopically expressed TL protein. The TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid and vigorous immunologic rejection of the allograft. In MLR studies, transgenic stimulator cells induced the proliferation of responders to a level intermediate between genetically identical and H-2-disparate responder-stimulator combinations. The TL protein was also capable of stimulating cytotoxic T lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further data demonstrated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell surface. Together, these data suggest that H-2T18(d) is capable of interacting with T cells via a bound peptide. These data further support the possibility that TL may subserve a specialized function within the immunologic system.",
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Sharma, P, Joyce, S, Chorney, KA, Griffith, JW, Bonneau, RH, Wilson, FD, Johnson, CA, Flavell, RA & Chorney, MJ 1996, 'Thymus-leukemia antigen interacts with T cells and self-peptides', Journal of Immunology, vol. 156, no. 3, pp. 987-996.

Thymus-leukemia antigen interacts with T cells and self-peptides. / Sharma, Padmanee; Joyce, Sebastian; Chorney, Karen A.; Griffith, James W.; Bonneau, Robert H.; Wilson, Frank D.; Johnson, Colena A.; Flavell, Richard A.; Chorney, Michael J.

In: Journal of Immunology, Vol. 156, No. 3, 01.02.1996, p. 987-996.

Research output: Contribution to journalArticle

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Sharma P, Joyce S, Chorney KA, Griffith JW, Bonneau RH, Wilson FD et al. Thymus-leukemia antigen interacts with T cells and self-peptides. Journal of Immunology. 1996 Feb 1;156(3):987-996.