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Characterization of a T cell receptor and its ligands

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Title: Characterization of a T cell receptor and its ligands
Author(s): Soo Hoo, William
Doctoral Committee Chair(s): Kranz, David M.
Department / Program: Biochemistry
Discipline: Biochemistry
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Biology, Molecular Biology, Cell Health Sciences, Immunology
Abstract: Cytotoxic T lymphocytes (CTL) recognize and lyse cells presenting viral or tumor-associated antigens associated with class I major histocompatibility complex proteins. Recognition occurs between the T cell receptor (TCR) and a complex of an antigenic peptide/major histocompatibility complex (MHC) product. In addition, the CD8 molecule of the CTL stabilizes the interaction by binding the constant domain of the MHC product. Clone 2C recognizes a peptide (p2C) bound to the MHC product L$\sp{\rm d}.$ L$\sp{\rm d}$ levels expressed by a panel of tumor cells directly correlated with their ability to be lysed and incubation of target cells with exogenous p2C led to increased lysis by CTL 2C which was inhibited minimally with anti-CD8 or anti-TCR antibodies. Thus at high ligand densities, very few TCR molecules/2C cell are needed for recognition.It has been observed previously that CTL bearing particular V$\beta$ chains recognize microbial enterotoxins bound to class II MHC products. Clone 2C as well as other CTL derived from polyclonal T cell populations were able to recognize staphylococcal enterotoxin B (SEB) bound to class II-expressing target cells. Recognition was inhibited by anti-TCR, LFA-1, and CD8 antibodies but not by antibodies against other cell surface determinants. The striking thing about these results is that, contrary to previous studies, CD8 is required by CTL for recognizing SEB-labeled target cells. Using polyclonal CTL, we have shown that this observation is also influenced by ligand density. Taken together, we propose that CD8 function is essential for virtually all CTL.A further study of CTL function requires the clarification of the binding properties of the TCR. The problem has been the difficulty in obtaining sufficient quantities of active receptor. To this end, a single-chain T cell receptor gene encoding the $\rm V\alpha/V\beta$ domains of 2C was expressed in E. coli linked by a flexible polypeptide. The refolded $\rm V\alpha V\beta$ protein was bound by anti-V$\beta$8 and anti-TCR antibodies, suggesting the protein assumes a native conformation. These single-chain proteins will be useful as immunogens for eliciting anti-TCR antibodies and in the study of TCR structure and function.
Issue Date: 1993
Type: Text
Language: English
URI: http://hdl.handle.net/2142/19713
Rights Information: Copyright 1993 Soo Hoo, William
Date Available in IDEALS: 2011-05-07
Identifier in Online Catalog: AAI9314942
OCLC Identifier: (UMI)AAI9314942
 

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