Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes: analysis by antibody blocking and selective trypsinization.
Open Access
- 1 December 1982
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 156 (6), 1711-1722
- https://doi.org/10.1084/jem.156.6.1711
Abstract
While it is well established that murine cytolytic T lymphocytes (CTL) express the Lyt-2/3 molecular complex on their surface, conflicting results have been reported concerning the role of this complex in CTL activity. This question was reinvestigated at the clonal level. Although different (H-2b anti-H-2d) CTL clones expressed comparable amounts of Lyt-2/3 molecules, as assessed by quantitative flow microfluorometry, the activity of some clones was inhibited by low doses (10 ng) of monoclonal anti-Lyt-2 or anti-Lyt-3 antibodies (in the absence of complement), whereas other clones were not inhibited by either antibody at doses as high as 5 .mu.g. Treatment of these clones with doses of trypsin sufficient to cleave Lyt-2/3 antigenic determinants from the cell surface resulted in a similar dissociation: clones that were inhibited by antibodies lost cytolytic activity, whereas uninhibited clones were unaffected by trypsin treatment. The dissociation observed among different alloreactive clones could be demonstrated within self-H-2-restricted (H-2b anti-MSV) clones exhibiting cross-reactivity with normal H-2d products. The lytic activity of these clones against the relevant syngeneic target cells was unaffected by anti-Lyt-2 antibodies or trypsin, whereas their cross-reactivity on H-2d target cells was abolished by either treatment. The results provide direct evidence for clonal heterogeneity in the requirement for Lyt-2/3 molecules in CTL-mediated lysis. The function of Lyt-2/3 molecules probably to stabilize the interaction between CTL receptors and the corresponding antigens on the target cells. The requirement for such a stabilization is apparently correlated with low number and/or affinity of CTL receptors.This publication has 23 references indexed in Scilit:
- Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. II. Analysis of the clonal progeny of CTL precursors stimulated in vitro with syngeneic tumor cells.The Journal of Immunology, 1980
- Interaction of Cytotoxic T Lymphocytes and Target CellsPublished by S. Karger AG ,1979
- Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus.The Journal of Experimental Medicine, 1979
- Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antiseraProceedings of the National Academy of Sciences, 1979
- T-cell lines which cooperate in generation of specific cytolytic activityNature, 1979
- SEQUENTIAL PRECIPITATION OF MOUSE THYMOCYTE EXTRACTS WITH ANTI-LYT-2 AND ANTI-LYT-3 SERA .1. LYT-2.1 AND LYT-3.1 ANTIGENIC DETERMINANTS RESIDE ON SEPARABLE MOLECULAR-SPECIES1978
- Cytotoxic T Lymphocyte Membrane Components: An Analysis of Structures Related to FunctionPublished by Springer Nature ,1977
- Early detection of potentially lethal events in T cell‐mediated cytolysisEuropean Journal of Immunology, 1975
- GENERATION OF CYTOTOXIC T LYMPHOCYTES IN VITROThe Journal of Experimental Medicine, 1974
- The cellular basis of immunologic memory.1971