The ability of Ia and H-2Kk-bearing membranes to replace the antigen-presenting cell in an H-2Kk allogeneic cytotoxic T cell response.
Induction of an allogeneic cytotoxic T lymphocyte (CTL) response is dependent, in part, on uptake and processing of the class I alloantigen by antigen-presenting cells and subsequent Ia-restricted recognition of the alloantigen by helper T cells, resulting in lymphokine production. The nature of the antigen-processing event has been investigated using reconstituted membranes to replace the antigen-presenting cells in the generation of a secondary allogeneic CTL response. Membranes were isolated from an Iad-positive antigen presenting B cell lymphoma (D2N), detergent solubilized and then reconstituted together with affinity-purified H-2Kk antigen in the presence of protease inhibitors. These reconstituted vesicles, containing both syngeneic Ia and alloantigen, were able to induce the helper T cell arm of the CTL response in cultures depleted of antigen-presenting cells. A variety of control experiments provided strong evidence that the helper T cells recognized the H-2Kk, probably in its native form, in an Ia-restricted manner on the vesicles, while the pre-CTL can directly recognize H-2Kk. Recognition was only effective if both the Ia and alloantigen were inserted into the same membrane bilayer. The results strongly suggest that the obligatory antigen processing event required for helper T cell recognition of alloantigen is simply the insertion of the alloantigen into the same membrane bilayer as the syngeneic Ia restricting element.
Weinberger
O
O
Herrmann
S H
SH
Greenstein
J L
JL
Mescher
M F
MF
Burakoff
S J
SJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008211:Lymphocyte Cooperation; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II