LFA-1-mediated antigen-independent T cell adhesion is regulated by CD4 and p56lck tyrosine kinase.
We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti-CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal-inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag-independent adhesion events of CD4+ T cells.
Mazerolles
F
F
National Institute of Health and Medical Research (INSERM) U 132, Necker Hospital for Sick Children, Paris, France.
Barbat
C
C
Meloche
S
S
Gratton
S
S
Soula
M
M
Fagard
R
R
Fischer
S
S
Hivroz
C
C
Bernier
J
J
Sekaly
R P
RP
D000328:Adult; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D016227:Benzoquinones; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D014162:Transfection
D016227:Benzoquinones; D015704:CD4 Antigens; D015798:HLA-DR1 Antigen; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)