Antigenic cross-reactivity between human leukemic cells and dinitrophenylated normal leukocytes

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• Dinitrofluorobenzene-modified normal human leukocytes (DNP-LK) can elicit antibody production.
• These antibodies exhibit leukoagglutinating activity against human leukemic cells (HLC) after absorption.

Purpose of the Study:

• To investigate the nature of antibodies produced against dinitrofluorobenzene-modified leukocyte membrane extracts.
• To determine if these antibodies target the dinitrofluorobenzene modification or induced neoantigens.

Main Methods:

• Generation of rabbit antisera against dinitrofluorobenzene-modified granulocytes (DNP-GM) and lymphocytes (DNP-LM).
• Cytotoxicity assays and passive hemagglutination tests using modified and unmodified cells and proteins.
• Absorption studies to remove specific antibody populations.

Main Results:

• Antisera against DNP-GM and DNP-LM were cytotoxic to HLC.
• Antisera specifically reacted with DNP-GM and DNP-LM, but not with unmodified leukocytes or dinitrofluorobenzene-conjugated proteins, indicating a lack of anti-DNP antibodies.
• DNP-LK did not absorb anti-DNP antibodies from relevant antisera.

Conclusions:

• Dinitrophenylation of leukocyte membranes induces neoantigens that cross-react with HLC antigens.
• Antibodies generated against these modified cells are primarily directed against the induced neoantigens, not the dinitrofluorobenzene moiety.
• This finding has implications for understanding immune responses to modified cells and potential therapeutic strategies.