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A novel trafficking signal within the HLA-C cytoplasmic tail allows regulated expression upon differentiation of macrophages
Journal article   Peer reviewed

A novel trafficking signal within the HLA-C cytoplasmic tail allows regulated expression upon differentiation of macrophages

Malinda R. Schaefer, Maya Williams, Deanna A. Kulpa, Pennelope K. Blakely, Anna Q. Yaffee and Kathleen L. Collins
The Journal of immunology (1950), Vol.180(12), pp.7804-7817
06/15/2008
DOI: 10.4049/jimmunol.180.12.7804
PMCID: PMC2440697
PMID: 18523244

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Abstract

MHC class I molecules (MHC-I) present peptides to CTLs. In addition, HLA-C allotypes are recognized by killer cell Ig-like receptors (KIR) found on NK cells and effector CTLs. Compared with other classical MHC-I allotypes, HLA-C has low cell surface expression and an altered intracellular trafficking pattern. We present evidence that this results from effects of both the extracellular domain and the cytoplasmic tail. Notably, we demonstrate that the cytoplasmic tail contains a dihydrophobic (LI) internalization and lysosomal targeting signal that is partially attenuated by an aspartic acid residue (DXSLI). In addition, we provide evidence that this signal is specifically inhibited by hypophosphorylation of the adjacent serine residue upon macrophage differentiation and that this allows high HLA-C expression in this cell type. We propose that tightly regulated HLA-C surface expression facilitates immune surveillance and allows HLA-C to serve a specialized role in macrophages.
Immunology Life Sciences & Biomedicine Science & Technology

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