Recognition of carcinoembryonic antigen peptide and heteroclitic peptide by peripheral blood T lymphocytes. Export

@article{citeulike:2998422, abstract = {The carcinoembryonic antigen (CEA)-derived peptide CAP1 and heteroclitic peptide CAP1-6D are stimulators of HLA-A*A0201 restricted CEA-specific T cells in vivo and in vitro. The goal of this study was to evaluate differences in T cell responses to peptide and modified peptide antigens from CEA. The heterogeneity of responses among individuals is potentially important for the design of future CEA-directed immunotherapy trials. Peripheral blood mononuclear cells from blood donors were stimulated with peptide, IL-2, and IL-7. Weekly, microcultures were restimulated with irradiated, autologous peptide-loaded peripheral blood mononuclear cells and expanded in IL-2. Established T cell lines were tested by cytokine release assays using peptide-loaded T2 targets. T cell avidity was measured by cytokine release using targets expressing diminishing concentrations of peptide. Fine specificities were measured using targets loaded with alanine-substituted CAP1 peptide. Tumor recognition was measured using HLA-A*A0201/CAP1-transduced COS tumor targets. Varied responses to CAP1 and CAP1-6D were seen among individuals. The immunogenicity of CAP1 or CAP1-6D was donor dependent. Many T cells recognized one peptide but did not cross-recognize the altered peptide. The avidities of T cell lines were moderate to low, and fine specificities were consistent with a narrow antigen-specific repertoire. CAP1-6D-based immune therapy may not be optimal in some patients with CAP1-specific precursors. The T cell repertoire may be a central contributor to the limited responses seen with CEA-directed immunotherapy to date. Treatment strategies designed to alter or expand the T cell repertoire against CEA should be considered for trials.}, address = {Department of Surgery, University of Chicago, IL, USA.}, author = {Brown, M. E. and Miao, H. and McKee, M. D.}, citeulike-article-id = {2998422}, citeulike-linkout-0 = {http://dx.doi.org/10.1097/CJI.0b013e31802b5005}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17414326}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17414326}, doi = {10.1097/CJI.0b013e31802b5005}, issn = {1524-9557}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, keywords = {avidity, cap1, cap1-6d, cea}, month = {April}, number = {3}, pages = {350--358}, posted-at = {2008-07-14 09:42:40}, priority = {2}, title = {Recognition of carcinoembryonic antigen peptide and heteroclitic peptide by peripheral blood T lymphocytes.}, url = {http://dx.doi.org/10.1097/CJI.0b013e31802b5005}, volume = {30}, year = {2007} }

TY - JOUR ID - citeulike:2998422 L3 - citeulike-article-id:2998422 N2 - The carcinoembryonic antigen (CEA)-derived peptide CAP1 and heteroclitic peptide CAP1-6D are stimulators of HLA-A*A0201 restricted CEA-specific T cells in vivo and in vitro. The goal of this study was to evaluate differences in T cell responses to peptide and modified peptide antigens from CEA. The heterogeneity of responses among individuals is potentially important for the design of future CEA-directed immunotherapy trials. Peripheral blood mononuclear cells from blood donors were stimulated with peptide, IL-2, and IL-7. Weekly, microcultures were restimulated with irradiated, autologous peptide-loaded peripheral blood mononuclear cells and expanded in IL-2. Established T cell lines were tested by cytokine release assays using peptide-loaded T2 targets. T cell avidity was measured by cytokine release using targets expressing diminishing concentrations of peptide. Fine specificities were measured using targets loaded with alanine-substituted CAP1 peptide. Tumor recognition was measured using HLA-A*A0201/CAP1-transduced COS tumor targets. Varied responses to CAP1 and CAP1-6D were seen among individuals. The immunogenicity of CAP1 or CAP1-6D was donor dependent. Many T cells recognized one peptide but did not cross-recognize the altered peptide. The avidities of T cell lines were moderate to low, and fine specificities were consistent with a narrow antigen-specific repertoire. CAP1-6D-based immune therapy may not be optimal in some patients with CAP1-specific precursors. The T cell repertoire may be a central contributor to the limited responses seen with CEA-directed immunotherapy to date. Treatment strategies designed to alter or expand the T cell repertoire against CEA should be considered for trials. IS - 3 JF - Journal of immunotherapy (Hagerstown, Md. : 1997) SN - 1524-9557 AD - Department of Surgery, University of Chicago, IL, USA. EP - 358 TI - Recognition of carcinoembryonic antigen peptide and heteroclitic peptide by peripheral blood T lymphocytes. VL - 30 SP - 350 KW - avidity KW - cap1 KW - cap1-6d KW - cea AU - Brown, ME AU - Miao, H AU - McKee, MD PY - 2007/04// UR - http://dx.doi.org/10.1097/CJI.0b013e31802b5005 ER -