Activated alpha4 integrins are preferentially expressed on immature thymocytes and activated T cells.
We have identified a novel mAb, SG31, which recognizes the mouse integrin alpha4 subunit. Unlike the epitopes recognized by other anti-alpha4 antibodies, the SG31 epitope is expressed on subpopulations of thymocytes and peripheral T cells. After manganese ion, but not phorbol myristic acetate activation, the epitope is induced and expressed on the majority of peripheral T cells. These data suggest that the SG31 epitope is an activation epitope and that manganese ions activate alpha4 integrins by inducing a conformational change. Comparative flow cytometric analyses showed that the SG31 epitope as well as the epitope detected by other anti-alpha4 antibodies is expressed on all B lineage cells. In the T lineage, expression of the alpha4 integrins is down-regulated during thymocyte development. Although mature thymocytes still express the alpha4 integrins, they lose almost entirely the activation epitope recognized by SG31. In contrast, the most immature thymocytes express high levels of this epitope. In the periphery, SG31 epitope is expressed mostly by activated T cells, in contrast to the overall population of T cells that express the alpha4 integrins at homogenous levels. These results suggest that the activation of the alpha4 integrins is parallel to that of T cells.
Shu
Fengyu
F
Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama at Birmingham, 378 Wallace Tumor Institute, 1824 6th Avenue South, Birmingham, AL 35294-3300, USA.
Holzmann
Bernhard
B
Seibold
Frank
F
Erle
David
D
Kearney
John F
JF
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D000939:Epitopes / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D066298:In Vitro Techniques; D039441:Integrin alpha4 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005353:Fibronectins; D039441:Integrin alpha4; D008345:Manganese; D013755:Tetradecanoylphorbol Acetate