CD8 beta increases CD8 coreceptor function and participation in TCR-ligand binding

To study the role of CD8 beta in T cell function, we derived a CD8 alpha/beta(-) (CD8(-/-)) T cell hybridoma of the H-2K(d)-restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8 alpha alone or together with CD8 beta. All three hybridomas released interleukin 2 upon incubation with L cells expressing K-d-peptide derivative complexes, though CD8 alpha/beta cells did so more efficiently than CD8 alpha/beta and especially CD8(-/-) cells. More strikingly, only CD8 alpha/beta cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab' fragments of the anti-K-d alpha 3 monoclonal antibody SF1-1.1.1 or substitution of K-d D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR-ligand binding on CD8 alpha/beta cells was similar to 5- and 20-fold more avid than on CD8 alpha/a and CD8(-/-) cells, respectively. SF1-1.1.1 Fab' or K-d mutation D227K reduced the TCR photoaffinity labeling on CD8 alpha/beta cells to approximately the same low levels observed on CD8(-/-) cells. These results indicate that CD8 alpha/beta is a more efficient coreceptor than CD8 alpha/alpha, because it more avidly strengthens TCR-ligand binding.