Jonathan P. Schneck, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Medicine
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Immunology; Member, Graduate Program in Pathobiology
Identification and characterization of T cell mediated immune responses and their immune signature are key elements to understanding the cellular immune response. A critical interaction that helps initiate and direct T cells is the interaction between a specific T cell receptor and a cognate antigen-Human Leukocyte Antigen (HLA) complex. My lab has had a long-term interest in characterizing and understanding this interaction using multiscale and multidimensional analyses of T cell responses. These studies have enhanced our insights into the basic biology of T cell response and ultimately may lead to development of novel therapeutic approaches.
A major focuse of the lab has been development of HLA-Ig based artificial Antigen Presenting Cell, aAPC, bead-based platform technologies used for expansion and analysis of antigen-specific murine and human T cells. This was has been supported by multiple NIH, DOD, and other grants. These studies provided the basis for the development of a “Lego-like” platform technology (Figure 1), which is an easy to assemble, reductionist, system in which different immunological signals can be attached to a central scaffold. We have used HLA-Ig based aAPC for: A-1 and A-3) T cell activation in vitro and in vivo, A-2) T cell diagnostic tool, B) depletion of unwanted T cells, and C) activation of NKT cells. Thus the potential applications of the HLA-Ig based aAPC include both positive and negative immunomodulatory effects on cellular immune responses in vitro and in vivo.
Perica K, Bieler JG, Edidin M, Schneck JP. Modulation of MHC binding by lateral association of TCR and coreceptor. Biophys J, 103(9):1890-8, 2013.
de Melo AB, Nascimento EJ, Braga-Neto U, Dhalia R, Silva AM, Oelke M, Schneck JP, Sidney J, Sette A, Montenegro SM, Marques ET. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-1 and -II binding motifs. PLoS Negl Trop Dis, 7(1):Jan. 31, 2013 (Epub ahead of print).
Webb TJ, Li X, Giuntoli RL 2nd, Lopez PH, Heuser C, Schnaar RL, Tsuji M, Kurts C, OelkeM, Schneck JP. Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer. Cancer Res, 72(15):3744-52, 2012.
Boyle S, Kolin DL, Bieler JG, Schneck JP, Wiseman PW, Edidin M. Quantum dot fluorescence characterizes the nanoscale organization of T cell receptors for antigen. Biophys J, 101(11):L57- 9, 2011.
Lee JB, Oelke M, Ramachandra L, Canaday DH, Schneck JP. Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors. Immun Ageing, 8(6):4-11, 2011.
Xiao Z, Mohamood AS, Uddin S, Gutfreund R, Nakata C, Marshall S, Schneck JP, Yagita H, Hamad AR. Inhibition of Fax ligand in NOD mice unmasks a protective role for IL-10 against insulitis development. Am J Pathol, 179(2):725-32, 2011.