Antigen Recognition by an Alloreactive T Lymphocyte Clone

Manning, Thomas Crellin

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Description

Title

Antigen Recognition by an Alloreactive T Lymphocyte Clone

Author(s)

Manning, Thomas Crellin

Issue Date

1998

Doctoral Committee Chair(s)

Kranz, David M.

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Health Sciences, Oncology

Language

eng

Abstract

In chapter two, the ability of CTL 2C to recognize thiol-modified peptide variants is analyzed. A method for the synthesis and screening of thiol-modified peptides that are recognized by T cells is presented. Chapter three continues the peptide variant approach with examination of the ability of clone 2C and its receptor to recognize altered peptide ligands involving amino acid substitutions in the center of the alloantigenic peptide. In chapter four, the energy of antigen recognition is mapped using soluble 2C TCR and the alanine-scanning mutagenesis technique. A majority of the binding energy for alloantigen recognition is derived from residues within the CDR 1 and 2 regions of the 2C TCR. Additional TCR mutants are analyzed in chapter five, including several which improve the affinity of the TCR for pMHC. Finally, in chapter six we have examined the ability of 2C TCR transgenic mice on a RAG knockout background to recognize and eliminate tumors bearing the L$\sp{\rm d}$ alloantigen. We show that tumor rejection in this system occurs independent of both B7 costimulatory molecules and CD4$\sp{+}$ helper T cells.

Graduation Semester

1998

Type of Resource

text

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