Genetic and immunochemical evidence for CD4-dependent association of p56lck with the alpha beta T-cell receptor (TCR): regulation of TCR-induced activation.
Recent observations suggest that the tyrosine kinase p56lck is involved in the transduction of transmembrane signals through the antigen specific T cell receptor (TCR) in CD4+ T cells. By means of in vitro kinase assays, we have found that p56lck coprecipitated with the TCR from lysates of a murine CD4+ T cell line in the absence of TCR-mediated stimuli. Analysis of CD4- mutants and CD4-transfected cells shows that p56lck-TCR association occurred only when CD4 was present. The functional importance of CD4:p56lck-TCR association was demonstrated by low activating potential of rare clonotypic antibodies which did not coprecipitate CD4:p56lck, as well as by total or partial loss of anti-TCR or antigen induced stimulation in CD4- cells, which could be recovered by CD4 transfection. Complementation assays using different anti-TCR antibodies suggest that cross linking of TCR-p56lck:CD4 plus structural changes in the complex are needed for efficient transduction of activating signals through the TCR in these cells.
Díez-Orejas
R
R
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Ballester
S
S
Feito
M J
MJ
Ojeda
G
G
Criado
G
G
Ronda
M
M
Portolés
P
P
Rojo
J M
JM
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D017252:CD3 Complex; D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)