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A novel co-stimulatory T cell antigen co-expressed on renal cell carcinoma
Authors:Labuda, Tord   Lando, Peter   Bjorkdahl, Olle   Kalland, Terje   Vessella, Robert   Hedlund, Gunnar   Eriksson, Hakan   Sjogren, Hans Olov   Dohlsten, Mikael
Affiliation:1 Department of Tumor Immunology, The Wallenberg Laboratory, University of Lund Box 7031, S-220 07 Lund Sweden
2 Pharmacia Oncology, Immunology, Scheelevagen 22, S-223 63 Lund Sweden
3 University of Washington, Seattle, WA 98195, USA
Abstract:The A6H mAb raised primarily against human renal cell carcinoma(RCC) has previously been shown to bind strongly to RCC, tosome degree to colon carcinoma but only marginally to a varietyof normal tissues. Immunohlstochemical analysis of RCC tissuescontaining tumor-Infiltrating lymphocytes revealed that A6Hstained both tumor cells and lymphocytes. FACS analysis of humanperipheral blood cells demonstrated that A6H mAb stained 85-90%of both CD4+ and CD8+ T cells, but not granulocytes, monocytes,NK cells or B cells. Furthermore, 85-90% of naive and memoryT helper cells were stained with A6H suggesting that the A6HmAb defines unique subsets within these T cell populations.Dual staining showed that A6H mAb bind to an antigen that isclearly distinct from other cell surface molecules on T cells,including CD28, CD29, CD26, CD44 and ICAM-2. A6H mAb bindinginduced a second signal in anti-CD3 mAb activated T cells, resultingIn cell proliferation, IL-2 receptor expression and vigorousproduction of IFN-{gamma} and TNF, and production of minor amountsof IL-2. Immunoprecipitatlon with A6H mAb indicated a molecularweight of 120-140 kDa on both T cells and RCC. We suggest thatthe A6H mAb defines a unique T cell surface antigen which isinvolved in signal transduction and is expressed on subsetsof human T cells. The co-expression of A6H on T cells and tumorcells suggests a possible function related to common propertiesof these cells.
Keywords:co-stimulation   renal cell carcinoma   T cell
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