Student Theses and Dissertations

Date of Award

1994

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Abstract

Superantigens such as staphylococcal enterotoxin B (SEB) have been widely used to study T cell tolerance. While both clonal deletion and apparent anergy have been described in response to superantigens, it has not been clear whether true anergy occurs, or whether the most reactive T cells are selectively deleted, leaving less reactive clones. To address this question, the response of an essentially monoclonal population of primary T cells to a superantigen was followed by priming ovalbumin (OVA) specific (X􁪽 T cell receptor transgenic mice with SEB. Cells from these mice appeared to be anergic in that they were hyporesponsive to OVA peptide as well as to SEB. The anergic cells could respond to PMA and ionomycin suggesting that a proximal signal transduction step was affected. Cells from transgenic mice primed with OVA peptide, the specific antigen, were not anergic. Thus, in this system, the ability to tolerize mature T cells appears to be a property unique to superantigens. To address the question of whether superantigen induced tolerance was due to T cell activation in the absence of costimulation, we examined the effect of the CD28/B7 pathway on the response of T cells to SEB and OVA. The T cell response to both OVA and SEB was enhanced by antibodies to the CD28 coreceptor suggesting that CD28/B7 mediated costimulation plays a role in the signal transduction pathways coupled to the two types of antigens.

Comments

A thesis submitted to the faculty of Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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