Ex Parte KALISH - Page 8


                Appeal No. 2002-1355                                                  Page 8                  
                Application No. 08/907,783                                                                    

                (e.g. monocytes, macrophages) are required.  The T2 cells are not functioning as              
                antigen presenting cells (which is to be expected since the T2 cells lack antigen             
                presenting Major Histocompatibility Complex antigens HLA-DR and HLA-A,B,C),                   
                but rather function as accessory cells.”  Page 14.                                            
                      In Yokozeki’s assay system, by contrast, the keratinocytes function as                  
                antigen-presenting cells.  See Yokozeki, page 394:  “We conducted a study on                  
                the primary in vitro activation of T cells from non-sensitized mice by using                  
                hapten-conjugated Pam 212 cells (keratinocyte cell line). . . . Monolayered Pam               
                212 cells were incubated with a variety of chemicals exhibiting allergic                      
                potential. . . .  T cells and macrophages . . . were cocultured for 5 days with those         
                monolayered Pam cells conjugated with chemicals.”  See also page 399:                         
                      [W]e examined whether or not primary activation of T cells from                         
                      nonsensitized Balb/c mice can be induced by hapten-conjugated                           
                      Pam cells and macrophages instead of hapten-conjugated                                  
                      Langerhans [dendritic] cells. . . .                                                     
                      The role of the Pam cells and macrophages in our system remains                         
                      unclear. . . . Fahr et al. recently suggested that keratinocyte (KC)-                   
                      derived protein but not 3T3-fibroblast-derived protein can serve as                     
                      antigenic carriers for hapten.  Our data are consistent with those of                   
                      Fahr et al.                                                                             
                      One possibility of the mechanism in our system is that                                  
                      macrophages may play a role as antigen-processing cell and be                           
                      required as the source of a costimulatory signal (2nd signal) and                       
                      the Pam cell[s] may serve as antigen carriers for hapten.  This                         
                      possibility is currently under investigation.                                           
                (Reference citations omitted.)                                                                










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