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Heterogeneity of cell surface structures involved in cytotoxicity mediated by lymphokine activated killer cells
1Department of Pathology, University of Southern California School of Medicine, Los Angeles.
Abstract:
Lymphokine activated killer (LAK) cells mediate the lysis of a variety of histologically distinct tumor targets. We investigated the nature and diversity of the structures involved in the recognition phenomenon by evaluating the effects of treating effector and target cells with trypsin and chymotrypsin, enzymes that disrupt surface protein molecules. Chymotrypsin and trypsin treatment of B16 target cells, a murine melanoma cell line, significantly abolished killing by LAK cells. Alternatively, neither of these treatments in P815 cells, a murine mastocytoma cell line, affected killing by LAK cells. Moreover, we found a differential effect of both these enzymes on YAC-1 cells, a murine leukemia cell line, with trypsin having a less inhibitory effect on cytolysis than chymotrypsin. The nature of the LAK cell receptor that presumably plays a role in binding target antigen was also investigated. Treatment of LAK cells with chymotrypsin significantly reduced lysis of the B16 and YAC-1 target cell types. However, trypsin treatment of the effectors only inhibited killing of the B16 tumor cell line. Cytotoxicity exerted against YAC-1 remained unaltered upon trypsinization of LAK cells. These cumulative results indicate heterogeneity of both the receptors on the LAK cells and the surface antigen molecules recognized on these targets. The use of YAC-1 as a target provided us with a tool to compare the LAK with the natural killer (NK) systems. The overall effect of proteolytic enzyme treatment in reducing cell lysis was more pronounced in the NK than in the LAK system.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Proteolytic enzymes reveal distinct surface molecules on tumor cells targeted by Lymphokine-Activated Killer (LAK) cells. This suggests varied LAK cell receptors and target antigens, impacting cancer immunotherapy research.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Lymphokine-activated killer (LAK) cells are crucial for tumor cell lysis.
- Understanding LAK cell recognition mechanisms is vital for cancer immunotherapy.
Purpose of the Study:
- To investigate the nature and diversity of surface molecules involved in LAK cell-tumor recognition.
- To differentiate LAK cell receptor and target antigen heterogeneity.
Main Methods:
- Treatment of effector (LAK) and target cells (B16 melanoma, P815 mastocytoma, YAC-1 leukemia) with trypsin and chymotrypsin.
- Evaluation of the effects of enzyme treatment on LAK cell-mediated cytotoxicity.
Main Results:
- Chymotrypsin and trypsin abolished LAK cell killing of B16 cells.
- P815 cells were unaffected by enzyme treatments.
- Trypsin had a less inhibitory effect than chymotrypsin on LAK cell lysis of YAC-1 cells.
- Chymotrypsin reduced LAK cell lysis of B16 and YAC-1 cells, while trypsin only inhibited B16 cell lysis.
- Proteolytic enzyme effects were more pronounced on Natural Killer (NK) cells than LAK cells.
Conclusions:
- Results indicate heterogeneity in both LAK cell receptors and recognized target surface antigens.
- YAC-1 cells serve as a useful tool for comparing LAK and NK cell systems.
- Findings contribute to understanding LAK cell-mediated tumor immunity and potential therapeutic strategies.