Abstract

The main objective of this renewal application is to define, at the molecular level, the antigenic sites on SV40 T antigen recognized by the cytotoxic T lymphocytes (CTL) in association with self coded major histocompatibility complex class I or class II glycoproteins. We have identified at least three distinct CTL recognition sites in the amino terminal half and one site in the carboxy terminal half of SV40 T antigen. Using CTL clones and SV40 deletion mutants, we are now proposing to, (1) determine the identify of amino acids in CTL recognition sites on T antigen and the influence of amino acids within the sites on CTL recognition in association with H-2 antigens; (2) analyses of antigenic loss variants that have escaped CTL mediated lysis for alteration in SV40 T antigen CTL recognition antigenic sites; (4) investigate the nature of T antigen recognized by CTL; and (5) study the contribution of individual antigenic sites to CTL mediated response. The approach utilized here will allow us to relate the role of SV40 T antigen in transformation and in inducing a CTL immune response to the antigenic sites on SV40 T antigen in the host undergoing oncogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA025000-14
Application #
3482003
Study Section
Virology Study Section (VR)
Project Start
1978-06-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
14
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033

  Publications

Memarnejadian, Arash; Meilleur, Courtney E; Shaler, Christopher R et al. (2017) PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8+ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination. J Immunol 199:3348-3359
Goodwin, Erin M; Zhong, Qing; Abendroth, Catherine S et al. (2013) Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse. Comp Med 63:338-41
Maleki Vareki, S; Harding, M J; Waithman, J et al. (2012) Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin. Am J Transplant 12:233-9
Tatum, Angela M; Watson, Alan M; Schell, Todd D (2010) Direct presentation regulates the magnitude of the CD8+ T cell response to cell-associated antigen through prolonged T cell proliferation. J Immunol 185:2763-72
Otahal, Pavel; Knowles, Barbara B; Tevethia, Satvir S et al. (2007) Anti-CD40 conditioning enhances the T(CD8) response to a highly tolerogenic epitope and subsequent immunotherapy of simian virus 40 T antigen-induced pancreatic tumors. J Immunol 179:6686-95
Otahal, Pavel; Schell, Todd D; Hutchinson, Sandra C et al. (2006) Early immunization induces persistent tumor-infiltrating CD8+ T cells against an immunodominant epitope and promotes lifelong control of pancreatic tumor progression in SV40 tumor antigen transgenic mice. J Immunol 177:3089-99
Otahal, Pavel; Hutchinson, Sandra C; Mylin, Lawrence M et al. (2005) Inefficient cross-presentation limits the CD8+ T cell response to a subdominant tumor antigen epitope. J Immunol 175:700-12
Barton, Lance F; Runnels, Herbert A; Schell, Todd D et al. (2004) Immune defects in 28-kDa proteasome activator gamma-deficient mice. J Immunol 172:3948-54
Schell, Todd D (2004) In vivo expansion of the residual tumor antigen-specific CD8+ T lymphocytes that survive negative selection in simian virus 40 T-antigen-transgenic mice. J Virol 78:1751-62
Staveley-O'Carroll, Kevin; Schell, Todd D; Jimenez, Marcela et al. (2003) In vivo ligation of CD40 enhances priming against the endogenous tumor antigen and promotes CD8+ T cell effector function in SV40 T antigen transgenic mice. J Immunol 171:697-707

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