Relative expression levels of the HLA class-I proteins in normal and HIV-infected cells.

J Immunol 2015 Apr 9;194(8):3594-600. Epub 2015 Mar 9.

Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139

The expression level of HLA class-I proteins is known to influence pathological outcomes: pathogens downregulate HLA to evade host immune responses, host inflammatory reactions upregulate HLA, and differences among people with regard to the steady-state expression levels of HLA associate with disease susceptibility. Yet precise quantification of relative expression levels of the various HLA loci is difficult because of the tremendous polymorphism of HLA. We report relative expression levels of HLA-A, HLA-B, HLA-C, and HLA-E proteins for the specific haplotype A*02:01, B*44:02, C*05:01, which were characterized using two independent methods based on flow cytometry and mass spectrometry. PBLs from normal donors showed that HLA-A and HLA-B proteins are expressed at similar levels, which are 13-18 times higher than HLA-C by flow cytometry and 4-5 times higher than HLA-C by mass spectrometry; these differences may reflect variation in the conformation or location of proteins detected. HLA-E was detected at a level 25 times lower than that of HLA-C by mass spectrometry. Primary CD4(+) T cells infected with HIV in vitro were also studied because HIV downregulates selective HLA types. HLA-A and HLA-B were reduced on HIV-infected cells by a magnitude that varied between cells in an infected culture. Averaging all infected cells from an individual showed HLA-A to be 1-3 times higher and HLA-B to be 2-5 times higher than HLA-C by flow cytometry. These results quantify substantial differences in expression levels of the proteins from different HLA loci, which are very likely physiologically significant on both uninfected and HIV-infected cells.

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http://www.jimmunol.org/content/early/2015/03/07/jimmunol.14
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http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.1403234
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http://dx.doi.org/10.4049/jimmunol.1403234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390493PMC
April 2015
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References

(Supplied by CrossRef)
Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains.
Jones et al.
J. Virol. 1995
Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression.
Bennett et al.
J. Immunol. 1999

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