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  • Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity.

Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity.

eLife (2018-07-11)
Brogan Yarzabek, Anita J Zaitouna, Eli Olson, Gayathri N Silva, Jie Geng, Aviva Geretz, Rasmi Thomas, Sujatha Krishnakumar, Daniel S Ramon, Malini Raghavan
ABSTRACT

The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by peptide loading complex (PLC) components is expected to ensure the cell surface expression of stable peptide-HLA class I complexes. This is exemplified by HLA-B*08:01 in primary human lymphocytes, with both expression level and half-life at the high end of the measured HLA-B expression and stability hierarchies. Conversely, low expression on lymphocytes is measured for three HLA-B allotypes that bind peptides with proline at position 2, which are disfavored by the transporter associated with antigen processing. Surprisingly, these lymphocyte-specific expression and stability differences become reversed or altered in monocytes, which display larger intracellular pools of HLA class I than lymphocytes. Together, the findings indicate that allele and cell-dependent variations in antigen acquisition pathways influence HLA-B surface expression levels, half-lives and receptivity to exogenous antigens.

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Monoclonal Anti-γ-Adaptin antibody produced in mouse, clone 100/3, ascites fluid