Evidence for a new HLA determinant that causes T cell activation without costimulation.
We describe the requirements for T cell activation by a mAb termed 4-10 that recognizes a novel determinant on MHC class I molecules. The determinant recognized by mAb 4-10 appears on resting T cells of all individuals tested (n greater than 30). Unlike previously described anti-class I mAb, 4-10 was shown to be directly mitogenic for T cells obtained from more than 20 normal donors. In order for 4-10 to exert its mitogenic effect on purified T cell populations it must be immobilized on a solid support. Immobilization of 4-10 can be circumvented if low numbers of adherent cells are added to the T cell cultures. mAb 4-10 preferentially activates the CD8+ T cell subset as judged by the fact that CD8+ T cells preferentially down-regulated their TCR after 4-10 activation and because CD4+ T cell activation with 4-10 requires approximately five times the concentration of mAb needed to reach comparable levels of activation observed with CD8+ T cells. We further observed that simultaneous cross-linking of class I and CD8 Ag by using 4-10 and anti-CD8 mAb almost completely abrogated the proliferative response of T cells when anti-CD8 was presented in immobilized form. In contrast, similar cross-linking with 4-10 and anti-CD4 diminished the response by about 20%. We also found that other anti-class I mAb were able to synergize in the activation of T cells with mAb 4-10 in a dose-dependent manner.
Bristol-Myers Squibb Company, Department of Immunology, Wallingford, CT 06492-7660.
R S
RS
Mittler
C A
CA
Fifer
P
P
Burbach
K
K
Edinger
P A
PA
Kiener
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens; D002118:Calcium / Q000378:metabolism; D000939:Epitopes / Q000032:analysis*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D011233:Precipitin Tests; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007140:Immunoglobulin Fab Fragments; D015375:Receptors, Interleukin-2; D002118:Calcium