Premium
Selective Immunomodulation: Utilization of CD29/VLA Molecules
Author(s) -
Morimoto Chikao,
Sato Toshiya,
Tachibana Kouichi
Publication year - 1996
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.1996.tb04554.x
Subject(s) - paxillin , vinculin , microbiology and biotechnology , population , chemistry , biology , focal adhesion , phosphorylation , medicine , environmental health
Accumulating evidence suggests that the VLA/ CD29 molecule plays an important role in T‐cell costim‐ulation, and CD4 + CD29/VLA + memory T cells play a key role in induction of CD8 killer effector T cells which are considered to be a major population involved in graft rejection. To target limited elements of the T‐lymphocyte population, we have described the preparation of a bi‐specific antibody‐toxin conjugate designed to target CD4 + CD29 + memory T cells. We also showed that the solid‐phase crosslinking of VLA‐4 by the antibody against this molecule or by its ligand, the CS‐1 region of fibronectin, stimulates tyrosine phosphorylation of 140, 120‐105, 80‐70, 60‐55, 50, and 45 kilodalton proteins. In addition, we identified the ppl40 protein as PLCγ, ppl20 protein as ppl25 FAK , pp70 and pp50 proteins as paxillin, and pp60‐55 proteins as pp59 fyn and pp56 lck , and pp45 as MAP kinase, respectively. Moreover, we demonstrated that ppl25 FAK is directly associated with paxillin. The paxillin binding domain of ppl25 FAK is homologous to the paxillin binding domain of vinculin. Mutations in the conserved amino acid residues between ppl25 FAK and vinculin result in the loss of paxillin‐binding activity. Because VLA/CD29 is preferentially expressed on CD4 memory T cells, the above described system will be used to develop a novel drug design for providing selective immunosuppression useful for organ transplantation. Key Words: Immunomodulation–Graft rejection– Transplantation.