MHC class I cross-talk with CD2 and CD28 induces specific intracellular signalling and leads to growth retardation and apoptosis via a p56(lck)-dependent mechanism.
Ligation of the major histocompatibility complex class I molecules (MHC-I) on human T lymphoma cells (Jurkat) initiates p56(lck)-dependent intracellular signalling events (phosphotyrosine kinase activity; [Ca(2+)](i)) and leads to augmented growth inhibition and apoptosis. MHC-I ligation in concert with ligation of CD2 or CD28 augments, changes or modifies the pattern of activation. Ligation of MHC-I and CD2 alone resulted in growth inhibition, whereas CD28 ligation alone had no effect on cell proliferation. Ligation of MHC-I together with CD2 augmented growth inhibition and enhanced the level of apoptosis. In parallel experiments with the p56(lck)-negative Jurkat mutant cell, JCaM1.6, cross-linking neither influenced cell signalling nor cellular growth functions, indicating a cardinal role of the src kinases in signal transduction via MHC-I, CD2 and CD28 molecules. The results presented here provide evidence for the involvement of MHC-I molecules in the modulation of signal transduction via the CD2 and CD28 costimulatory molecules.
Ruhwald
M
M
Laboratory of Experimental Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Pedersen
A E
AE
Claesson
M H
MH
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000502:physiology*; D018801:CD2 Antigens / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology*; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000502:physiology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D002118:Calcium; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000099192:CD69 Antigens