Research Activities

Sandra M Hayes, Ph.D. Assistant Professor of Microbiology and Immunology 2220 Weiskotten Hall Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-7692

Education and Clinical Training

Research Program and Department Affiliations

Research Interests

Research Abstract

The T cell antigen receptor complex (TCR) is organized into two functional domains: an antigen-binding clonotypic heterodimer and a signal transducing complex composed of invariant CD3γ, -δ, -ε, and TCRζ chains. In all jawed vertebrates there are two different clonotypic heterodimers (TCRαβ and TCRγδ), which define the αβ and γδ T cell lineages, respectively. αβ- and γδTCRs also differ in the subunit composition of their signal transducing complexes, in that αβTCRs contain both CD3γε and CD3δε dimers, while γδTCRs contain only CD3γε dimers. Interestingly, stimulation of the γδTCR is not impaired despite the absence of CD3δ. In fact, comparison of the signaling potential of the two TCRs indicates that the γδTCR transduces signals better than the intact αβTCR, as measured by its ability to induce calcium mobilization, ERK activation and cellular proliferation. Collectively, these observations reveal a fundamental difference in the primary structure and signaling potential of αβ- and γδTCR complexes. This discovery impacts greatly on our perception of γδ T cells and, consequently, calls for a revision in our present understanding of T cell development and function.

The focus of this laboratory is to explore the structure-function relationship of the γδTCR complex. γδ T cells are purported to be the first line of defense, as the majority of them are located in epithelial tissues, where most pathogens invade the host. Our data support this theory, as the enhanced signaling proficiency of the γδTCR may enable γδ T cells to respond rapidly during an immune response. One aim of the lab is to determine how signal transduction by the γδTCR is superior to that of the αβTCR. We will use multiple techniques to identify whether differences in TCR subunit composition, stoichiometry and/or signal transduction pathways can provide a mechanism by which the γδTCR is capable of signaling better than the αβTCR.

We observe changes in the subunit composition of the γδTCR following in vitro activation and expansion. The FcεR1γ (FcRγ) chain, a signaling molecule found in some Fc and natural killer cell receptors, is included in the γδTCR, either as a homodimer or as a heterodimer with TCRζ. A second aim of the lab will be to study the effect of the activation-induced changes in the structure of the γδTCR on γδTCR signaling potential. An in vitro culture system that selects for γδ T cells that contain FcRγ in their TCR complexes will be used to compare directly signal transduction by γδTCRs containing TCRζ with those containing FcRγ in order to determine whether inclusion of FcRγ in the γδTCR alters the signaling potential of the γδTCR complex. Importantly, the changes that occur in the subunit composition of the γδTCR may influence γδ T cell effector functions and/or fate during an immune response. Using bacterial and viral model systems, in which γδ T cells are activated and expanded (such as Listeria, influenza and vaccinia), we will determine whether changes occur in vivo in the structure of the γδTCR during an immune response and whether these changes correlate with distinct effector functions and fates.

Selected References

Hayes, S.M., A. Sirr, S. Jacob, G.K. Sim and A. Augustin. 1996. Role of IL-7 in the shaping of the pulmonary γδ T cell repertoire. J. Immunol. 156:2723.

Hayes, S.M. and Love, P.E. 2002. Distinct structure and signaling potential of the γδTCR complex. Immunity 16:827-838.

Hayes, S.M., Laky, K., El-Khoury, D., Kappes D.J., Fowlkes B.J. and P.E. Love. 2002. Activation-induced modification in the CD3 complex of the γδ T cell receptor. J. Exp. Med. 196:1355-1361.

Hayes, S.M., Shores, E.W. and P.E. Love. 2003. An architectural perspective on signaling by the pre-, αβ and γδ T cell receptors. Immunol. Rev. 191:28-37.

Hayes, S.M., Li, L.Q. and P.E. Love. TCR signal strength influences αβ/γδ lineage fate. 2005. Immunity 22:582-593.

Hayes, S.M. and P.E. Love. Stoichiometry of the murine γδ T cell receptor. 2006. J. Exp. Med. 203:47-52.

Hayes, S.M. and P.E. Love. Strength of signal: A fundamental mechanism for cell fate specification. 2006. Immunol. Rev. 209:170-175.

Hayes, S.M. and P.E. Love. A retrospective on the requirements for γδ T cell development. 2007. Immunol. Rev. 215:8-14.

Laird, R.M. and S.M. Hayes. Profiling of the early transcriptional response of murine γδ T cells following TCR stimulation. 2009. Mol. Immunol. Doi:10.1016/j.molimm.2009.03.029.

This profile was last updated on 06/03/2009

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