HLA-DR molecules enhance signal transduction through the CD3/Ti complex in activated T cells

TY - JOUR

T1 - HLA-DR molecules enhance signal transduction through the CD3/Ti complex in activated T cells

AU - Odum, Niels

AU - Martin, P J

AU - Schieven, G L

AU - Masewicz, S

AU - Hansen, J A

AU - Ledbetter, J A

N1 - Keywords: Antibodies, Monoclonal; Antigens, CD; Antigens, CD3; Antigens, CD45; Antigens, Differentiation, T-Lymphocyte; Calcium; Cells, Cultured; HLA-DR Antigens; Histocompatibility Antigens; Humans; Lymphocyte Activation; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes

PY - 1991

Y1 - 1991

N2 - Crosslinking HLA-DR molecules by monoclonal antibodies (mAb) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic Ca2+ concentration ([Ca2+]i) in activated human T cells. Here we have studied the effect of DR on CD3-induced signal transduction in allospecific T-cell clones and T-leukemia (HUT78) cells. Co-crosslinking of DR with CD3 produced an enhanced [Ca2+]i response compared to that seen with CD3 alone. In contrast, CD2 responses were not enhanced by co-crosslinking with DR. Co-crosslinking CD45 in a tri-molecular complex of CD45, CD3, and DR completely abrogated the enhancing effects of DR on CD3-induced [Ca2+]i responses. In contrast, the enhancing effect of co-crosslinking CD4 on CD3 responses was not inhibited by co-crosslinking CD45. Thus, the DR-mediated accessory signals appear to be regulated differently from those provided by CD4 accessory molecules. The present data confirm, at the level of second messengers, recent findings suggesting that DR molecules have accessory functions in CD3/Ti-mediated T-cell responses.

AB - Crosslinking HLA-DR molecules by monoclonal antibodies (mAb) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic Ca2+ concentration ([Ca2+]i) in activated human T cells. Here we have studied the effect of DR on CD3-induced signal transduction in allospecific T-cell clones and T-leukemia (HUT78) cells. Co-crosslinking of DR with CD3 produced an enhanced [Ca2+]i response compared to that seen with CD3 alone. In contrast, CD2 responses were not enhanced by co-crosslinking with DR. Co-crosslinking CD45 in a tri-molecular complex of CD45, CD3, and DR completely abrogated the enhancing effects of DR on CD3-induced [Ca2+]i responses. In contrast, the enhancing effect of co-crosslinking CD4 on CD3 responses was not inhibited by co-crosslinking CD45. Thus, the DR-mediated accessory signals appear to be regulated differently from those provided by CD4 accessory molecules. The present data confirm, at the level of second messengers, recent findings suggesting that DR molecules have accessory functions in CD3/Ti-mediated T-cell responses.

M3 - Journal article

C2 - 1835188

SN - 2059-2302

VL - 38

SP - 72

EP - 77

JO - HLA

JF - HLA

IS - 2

ER -