The Journal of Immunology, Vol 145, Issue 3 794-803, Copyright © 1990 by American Association of Immunologists

ARTICLES

Evidence for a new HLA determinant that causes T cell activation without costimulation

RS Mittler, CA Fifer, P Burbach, K Edinger and PA Kiener
Bristol-Myers Squibb Company, Department of Immunology, Wallingford, CT 06492-7660.

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.

This article has been cited by other articles:

				L. Genestier, R. Paillot, N. Bonnefoy-Berard, G. Meffre, M. Flacher, D. Fevre, Y. J. Liu, P. Le Bouteiller, H. Waldmann, V. H. Engelhard, et al. Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I alpha 1 Domain Blood, November 1, 1997; 90(9): 3629 - 3639. [Abstract] [Full Text] [PDF]