Abstract

Analyses of human effector T cell repertoire in renal allograft rejection indicate that responses to a particular alloantigen, or a number of alloantigens, do not utilize all the available repertoire, but that some T cells have a selective advantage giving rise to predominant clonotypes. The advantage appears to be a result of an expression of a particular T cell antigen receptor beta chain gene. Using T cell lines established from lymphocytes infiltrating a rejected allograft, we propose to clone and sequence the predominant TcR beta chain gene to understand the molecular basis for their selection. The long term goals of this project are to use this knowledge to design ways of specifically eliminating or down-regulating the selected clonotypes in order to achieve prolonged graft survival. The immediate benefit of this project will be a greater understanding of the relationship between the structure of the T cell antigen receptor and its function in the recognition of antigen/MHC or foreign antigen alone.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI026935-01
Application #
3141013
Study Section
Immunobiology Study Section (IMB)
Project Start
1988-09-30
Project End
1991-08-31
Budget Start
1988-09-30
Budget End
1989-08-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Finn, O J; Debruyne, L A; Bishop, D K (1996) T cell receptor (TCR) repertoire in alloimmune responses. Int Rev Immunol 13:187-207
Hall, B L; Hand, S L; Alter, M D et al. (1993) Variables affecting the T cell receptor V beta repertoire heterogeneity of T cells infiltrating human renal allografts. Transpl Immunol 1:217-27
Finn, O J (1992) Pancreatic tumor antigens: diagnostic markers and targets for immunotherapy. Important Adv Oncol :61-77
Hall, B L; Finn, O J (1992) PCR-based analysis of the T-cell receptor V beta multigene family: experimental parameters affecting its validity. Biotechniques 13:248-57
Hall, B L; Finn, O J (1992) T cell receptor V beta gene usage in allograft-derived cell lines analyzed by a polymerase chain reaction technique. Transplantation 53:1088-99
Hand, S L; Hall, B L; Finn, O J (1992) T cell receptor V beta gene usage in HLA-DR1-reactive human T cell populations. The predominance of V beta 8. Transplantation 54:357-67
Jerome, K R; Barnd, D L; Bendt, K M et al. (1991) Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. Cancer Res 51:2908-16
Persons, D A; Owen, R D; Ostrowski, M C et al. (1991) Protein kinase C gamma expression mimics phorbol ester-induced transcriptional activation of a murine VL30 enhancer element. Cell Growth Differ 2:7-14
Finn, O J; Persons, D A; Bendt, K M et al. (1991) Retroviral transduction of protein kinase C-gamma into cytotoxic T lymphocyte clones leads to immortalization with retention of specific function. J Immunol 146:1099-103
Hand, S L; Hall, B L; Finn, O J (1990) T-cell receptor gene usage and expression in renal allograft-derived T-cell lines. Hum Immunol 28:82-95

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