Dual role of the CD44 molecule in T cell adhesion and activation.
Studies of T cell adhesion and activation reveal two new functions of the CD44 molecule, a molecule now recognized to be identical to three molecules of functional interest: Pgp-1, Hermes, and extracellular matrix receptor type III (ECMRIII). By screening for mAb which inhibit T cell adhesion to E, we have identified a functionally unique CD44-specific mAb, NIH44-1, which partially inhibits T cell rosetting by binding to CD44 on the E. NIH44-1, which immunoprecipitates a protein of 85 to 110 kDa with broad tissue distribution, was determined to be specific for CD44 based on comparison of its tissue distribution with multiple CD44-specific reference mAb and sequential immunoprecipitation with such mAb. Anticipating a role for many adhesion molecules in signal transduction, we studied the effect of CD44 mAb on T cell activation and observed that CD44 mAb dramatically augments T cell proliferation induced by CD3- and CD2-receptor-mediated activation. The augmentation of the response to immobilized CD3 mAb by exhaustively monocyte-depleted T cells indicates that augmentation can be mediated by binding to the T cell. Thus, our studies demonstrate specific new roles for CD44 in T cell adhesion and activation. Furthermore, we suggest that: 1) CD44 has a role in adhesion of cells of multiple lineages; and 2) CD44 may participate in adhesion not (only) by functioning as an adhesion receptor but rather by serving as an anchorage site for other adhesion molecules.
Shimizu
Y
Y
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Van Seventer
G A
GA
Siraganian
R
R
Wahl
L
L
Shaw
S
S
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000918:Antibody Specificity; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D001667:Binding, Competitive; D002448:Cell Adhesion; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016201:Receptors, Lymphocyte Homing; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016201:Receptors, Lymphocyte Homing