Inability of CD8 alpha' polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo.
T-cell accessory molecules, particularly CD4 and CD8, seem to be involved in the control of T-cell activation by antigen. Precisely how such molecules operate is not fully understood, but evidence to date suggests a dual role, as receptors binding ligands on stimulator cells and by direct or indirect involvement in intracellular signalling events. In mouse, truncated 'tailless' CD8 molecules occur naturally (CD8 alpha' polypeptides) and although they are expressed on the surface of thymocytes, they are not expressed on the surface of mature T cells. In this study, we show that truncated CD8 molecules are impaired in their ability to interact with the protein tyrosine kinase, p56lck, and have decreased ability to restore immune responsiveness in vitro. Our data support a dual function for CD8 molecules correlated with expression of external domains and cytoplasmic domains, respectively. Both functions appear to be critical for a competent immune system in vivo.
Zamoyska
R
R
Imperial Cancer Research Fund Tumour Immunology Unit, University College London, UK.
Derham
P
P
Gorman
S D
SD
von Hoegen
P
P
Bolen
J B
JB
Veillette
A
A
Parnes
J R
JR
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens; D002460:Cell Line; D006825:Hybridomas; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000502:physiology*; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)