Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function

Détails

ID Serval
serval:BIB_F2B5D1797CA7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function
Périodique
Journal of Experimental Medicine
Auteur⸱e⸱s
Moretta  A., Pantaleo  G., Mingari  M. C., Moretta  L., Cerottini  J. C.
ISSN
0022-1007 (Print)
Statut éditorial
Publié
Date de publication
03/1984
Volume
159
Numéro
3
Pages
921-34
Notes
Journal Article --- Old month value: Mar 1
Résumé
In an attempt to define the requirement of T8, T4, and T3 surface molecules in functional interactions occurring between human cytolytic T lymphocytes (CTL) and specific target cells, we have analyzed a large number of CTL clones derived from primary mixed lymphocyte culture (MLC) T cell populations for their susceptibility to inhibition by monoclonal antibodies (mAb) directed against these surface antigens. In most experiments, MLC T cells were stained with B9.4 (anti-T8) or OKT4 (anti-T4) mAb, separated into positive and negative cells using a fluorescence-activated cell sorter (FACS) and cloned under limiting conditions. While the lytic activity of the majority of T8+ CTL clones was inhibited by B9.4 mAb, approximately 15% of these clones were unaffected even in the presence of excess antibody. Flow cytofluorometric analysis of T8 antigen in individual clones did not show any correlation between the amount of T8 antigen expressed, the magnitude of cytolytic activity and the susceptibility (or lack thereof) to inhibition by B9.4 mAb. Of the 16 T4+ CTL clones analyzed, 7 were resistant to inhibition by OKT4 mAb even at doses 10-fold higher than that sufficient for complete inhibition of susceptible clones. Again, no correlation was found between the amount of T4 antigen expressed and the susceptibility to inhibition by the corresponding antibody. The same sets of T8+ and T4+ CTL clones were also analyzed for their susceptibility to inhibition by OKT3 mAb. Although all of the clones expressed the T3 surface antigen, only 15/23 T8+ clones and 9/14 T4+ clones were inhibited by anti-T3 mAb. To further document this clonal heterogeneity, we selected two T3+ T4- T8+ CTL clones that had no concomitant NK-like activity. One clone was resistant to inhibition by OKT3 mAb, whereas the other was highly susceptible. Incubation with OKT3 mAb resulted in modulation of the T3 molecules in both clones. Following modulation, however, the cytolytic activity of the resistant clones was unaffected, whereas the lytic activity of the susceptible clone was abrogated. These results thus indicate extensive clonal heterogeneity in the requirement for T3, T4, and T8 molecules in CTL function. Moreover, it appears that T3 molecules are not always physically and functionally linked to CTL receptor structures.
Mots-clé
Antibodies, Monoclonal/immunology/physiology Antigens, Differentiation, T-Lymphocyte Antigens, Heterophile/*immunology Antigens, Surface/*genetics/immunology Binding, Competitive Clone Cells/classification/immunology/metabolism *Cytotoxicity, Immunologic Humans Receptors, Antigen, T-Cell/genetics/physiology T-Lymphocytes, Cytotoxic/*classification/immunology/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:14
Dernière modification de la notice
20/08/2019 16:19
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