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Increases CD8 Coreceptor Function and
Participation in TCR-Ligand Binding
By


From the * Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale, Centre
National de la Recherche Scientifique de Marseille-Luminy, Case 906, 13288 Marseille, Cedex 09, France; and To study the role of CD8
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
in T cell function, we derived a CD8
/
(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
alone or together with CD8
. All three hybridomas released
interleukin 2 upon incubation with L cells expressing Kd-peptide derivative complexes, though
CD8
/
cells did so more efficiently than CD8
/
and especially CD8
/
cells. More strikingly, only CD8
/
cells were able to recognize a weak agonist peptide derivative variant.
This recognition was abolished by Fab
fragments of the anti-Kd
3 monoclonal antibody SF11.1.1 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
/
cells was ~5- and 20-fold more avid than on CD8
/a and CD8
/
cells, respectively. SF1-1.1.1 Fab
or Kd mutation D227K reduced the TCR photoaffinity labeling on
CD8
/
cells to approximately the same low levels observed on CD8
/
cells. These results
indicate that CD8
/
is a more efficient coreceptor than CD8
/
, because it more avidly
strengthens TCR-ligand binding.
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