Requirement for recognition of class II molecules and processed tumor antigen for optimal generation of syngeneic tumor-specific class I-restricted CTL.
The roles of Class II-restricted L3T4+ T cells and of accessory cells (AC) during the in vitro generation of Class I-restricted Lyt-2+ cytotoxic T cells (CTL) specific for a Class II-negative syngeneic tumor cell line, FBL, was examined. Treatment of responder FBL-immune spleen cells with alpha L3T4 plus complement before culture, as well as the direct addition of alpha L3T4 to cultures, diminished the generation of FBL-specific CTL. The contribution of L3T4+ cells could be completely replaced by the addition of exogenous cytokines. The data demonstrate that the optimal generation of FBL-specific Lyt-2+ CTL requires the presence of L3T4+ cells, presumably to provide necessary lymphokines. FBL-specific CTL could not be generated from purified FBL-immune T cells in the absence of AC. Syngeneic Ia+ macrophages (M phi), added at the initiation of culture, restored the response of purified T cells. Pretreatment of M phi with ammonium chloride or chloroquine, or the addition of monoclonal alpha I-Ab antibody at the initiation of culture, inhibited the ability of M phi to reconstitute the CTL response. Finally, the addition of exogenous helper factors could replace M phi and reconstitute the FBL-specific response of AC-depleted immune T cells. These results suggest that during the generation of Lyt-2+ CTL to a syngeneic tumor expressing only Class I MHC antigens, Ia+ AC are required to biochemically process antigen released from the tumor cells and present this modified antigen to Class II-restricted T helper cells.
D E
DE
Kern
J P
JP
Klarnet
M C
MC
Jensen
P D
PD
Greenberg
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D002450:Cell Communication; D000939:Epitopes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D015846:Monokines; D011506:Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D015846:Monokines; D011506:Proteins