Identification of 5 topographic domains of the mouse LFA-1 molecule: subunit assignment and functional involvement in lymphoid cell interactions.
We have evaluated the serologic and T cell function inhibiting properties of 10 rat mAb reactive with the mouse LFA-1 molecule. Binding inhibition studies revealed that these mAb identified five topographic domains on LFA-1, including an immunodominant epitope region (A) defined by 6 mAb (H35-89, H68-96, H85-326, H129-37, H154-595, and H155-141) and four other spatially separate epitopes each defined by a single mAb (i.e., B, H154-266; C, H129-296; D, H154-163; and E, H155-78). Immunoprecipitation studies carried out with T cell hybridoma detergent lysate containing native or dissociated alpha and beta LFA-1 subunits permitted assignment of the epitopes A, C, and D to the alpha-chain, while expression of the epitopes B and E required homologous pairing of the alpha and beta LFA-1 subunits. These anti-LFA-1 mAb did not bind to the Mac-1 positive P388D1 cells. All the six mAb directed at epitope A inhibited, in the range of 50 to 95%, the proliferative responses of alloantigen- or soluble-antigen GAT-specific T cell clones and the cytolytic activity of I-Ak-specific CTL clones. MAb reactive with the epitopes C and D also blocked these T cell responses, although to a lesser extent. No inhibition was observed with mAb specific to epitope B, whereas the epitope E-specific mAb H155-78 potentiated control T cell responses by 20 to 40%. Suboptimal amounts of anti-L3T4 mAb H129-19 were found to synergistically enhance the T cell function inhibiting properties of mAb to LFA-1 epitopes A, C, and D. These studies reveal an unexpected diversification of LFA-1 between mouse and rat species and further the functional dissection of this molecule.
Pont
S
S
Naquet
P
P
Marchetto
S
S
Regnier-Vigouroux
A
A
Blanc
D
D
Pierres
A
A
Pierres
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology*; D000939:Epitopes; D007518:Isoantibodies / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen; D051379:Mice; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007518:Isoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen