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*
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115;
Institut National de la Santé et de la Recherche Médicale, Unit 448, Faculte de Medicine de Creteil, Paris, France; and
Gastroenterology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
Expression of the BY55 protein has been shown to be tightly
associated with NK and CD8+ T lymphocytes with cytolytic
effector activity. To determine the function of this protein, we
molecularly cloned BY55 cDNA. The cDNA sequence predicts a
cysteine-rich, glycosylphosphatidylinositol-anchored protein of 181
amino acids with a single Ig-like domain weakly homologous to killer
inhibitory receptors. Reduction and carboxyamidomethylation of
immunoprecipitated BY55 gave a band of 27 kDa, whereas reduction alone
led to an 80-kDa species, suggesting that BY55 is a tightly
disulfide-linked multimer. RNA blot analysis revealed BY55 mRNAs of 1.5
and 1.6 kb whose expression was highly restricted to NK and T cells.
BY55 was expressed on the CD56dim, CD16+ subset
of NK cells, which have high cytolytic activity, but was not expressed
and was not induced on the CD56bright, CD16-
subset of NK cells, a subset with high proliferative, but low
cytolytic, capacity. In human tissues, BY55 mRNA was expressed only in
spleen, PBL, and small intestine (in gut lymphocytes). BY55 was
expressed on all intestinal intraepithelial lymphocytes, which were
predominantly
CD3+TCR
/ß+CD4-CD8+CD11b+CD28-CD45RO+CD56-CD101+CD103+
(Eß7 integrin). In addition, BY55 was
expressed on most CD8+CD28- peripheral blood T
cells. These phenotypic relationships suggest that
CD8+CD28+ precursor CTL may terminally
differentiate into CD8+CD28-BY55+
effector CTL and that some of the peripheral blood
CD8+CD28- subset may represent recirculation
from mucosal epithelial immune sites.
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