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-2Kd-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 Kd-peptide derivative complexes, though CD8 alpha/beta cells did so more efficiently than CD8 alpha/alpha 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-Kd alpha 3 monoclonal antibody SF1-1.1.1 or substitution of Kd 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 approximately 5- and 20-fold more avid than on CD8 alpha/a and CD8-/- cells, respectively. SF1-1.1.1 Fab' or Kd 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 CD8alpha/alpha, because it more avidly strengthens TCR-ligand binding.
Renard
V
V
Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille-Luminy, France.
Romero
P
P
Vivier
E
E
Malissen
B
B
Luescher
I F
IF
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma; D013953:Thymus Neoplasms
D016827:CD8 Antigens; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan