MHC class I is functionally associated with antigen receptors in human T and B lymphomas.
We have studied the antibody-induced effect of cross-linking the major histocompatibility complex class I (MHC-I) in human T leukemic cells (Jurkat) and human B lymphoma cells (Solubo, Burkitts lymphoma) on intracellular [Ca2+]i levels. The increase in [Ca2+]i after MHC-I cross-linking in Jurkat cells and Solubo cells was dependent on both intra- and extracellular Ca2+ stores. The initial increase was dependent on intracellular stores but the long-term elevated [Ca2+]i level was due to an influx of Ca2+. The kinetics of Ca2+ release and influx was different in the two cell lines. In both cell lines the increase in [Ca2+]i after MHC-I cross-linking caused upregulation of CD69, an early marker of activation. When studying the effect of MHC-I cross-linking on the TCR- and B cell antigen receptor (BCR)- mediated increase in [Ca2+]i, respectively, we observed that MHC-I had a costimulatory effect on the TCR-mediated increase in [Ca2+]i in Jurkat cells but not on the anti-IgM-mediated activity of Solubo cells. Studies of subpopulations of Jurkat and Solubo cells expressing different levels of MHC-I on their cell surfaces revealed that the TCR- and BCR-mediated increases in [Ca2+]i, respectively, were positively correlated with the level of MHC-I expressed on the cell surface. These observations suggest two different roles in signal transduction for the MHC-I molecules in the T and B cells studied. First, by themselves MHC-I complexes are able to induce activation of intracellular second messenger systems following cross-linking. Second, threshold levels for activation through antigen receptors in T and B cells are dependent on or determined by the actual numbers of MHC-I complexes present in the cell membrane. Thus the present data strongly point to a new, physiological role for MHC-I molecules in T and B cells.
Pedersen
A E
AE
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Jacoby
B F
BF
Skov
S
S
Claesson
M H
MH
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens