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Predominant HLA-class II bound self-peptides of a hematopoietic progenitor
cell line are derived from intracellular proteins
PE Harris, A Maffei, AI Colovai, J Kinne, S Tugulea and N Suciu-Foca
Department of Pathology, College of Physicians and Surgeons of Columbia
University, New York, NY, USA.
Human myeloid progenitor cells temporarily express HLA class II molecules
during the differentiation pathway to granulocytes and macrophages. The
significance of major histocompatibility complex (MHC) class II molecules
at this stage of development is unknown. As a first stop of inquiry into
their function, we have characterized the profile of major self-peptides
bound to the HLA-DR molecules expressed by KG-1 cells, a line that shares
many of the phenotypic characteristics of colony-forming
unit-granulocyte-macrophage progenitors. Searches of protein data bases
showed that all matching peptides bound to the HLA- DR molecules of KG-1
cells corresponded to intracellular, rather than exogenous or
transmembrane, precursor proteins. Because the absence of a conventional
self-peptide repertoire could be related to altered trafficking of class II
molecules, the biosynthesis of HLA-DR and the invariant chain proteins was
determined. The MHC class II associated invariant chain protein is
synthesized normally in KG-1 cells, but processed fragments of invariant
chain, class II-associated invariant chain peptides (CLIPs), occupy the
antigen-binding groove of KG-1 class II molecules at a much lower frequency
compared with that of mature antigen-presenting cells. Low CLIP occupancy
of HLA-DR is a characteristic shared by KG-1 cells, normal CD34+ progenitor
cells, and HLA-DR+ breast carcinoma cells. The unusual profile of MHC class
II bound peptides and the low level of CLIP bound to HLA-DR suggest that
the antigen-processing pathway of KG-1 is different from that characterized
in professional antigen-presenting cells and that exogenous
antigen-processing may be a developmentally acquired characteristic in the
myeloid lineage.
Volume 87,
Issue 12,
pp. 5104-5112,
06/15/1996
Copyright © 1996 by The American Society of Hematology
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