TY - JOUR TI - Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity AU - Yarzabek, Brogan AU - Zaitouna, Anita J AU - Olson, Eli AU - Silva, Gayathri N AU - Geng, Jie AU - Geretz, Aviva AU - Thomas, Rasmi AU - Krishnakumar, Sujatha AU - Ramon, Daniel S AU - Raghavan, Malini A2 - Bjorkman, Pamela J VL - 7 PY - 2018 DA - 2018/07/10 SP - e34961 C1 - eLife 2018;7:e34961 DO - 10.7554/eLife.34961 UR - https://doi.org/10.7554/eLife.34961 AB - 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. KW - HLA-B KW - MHC class I KW - half-life KW - expression KW - peptidome KW - transporter associated with antigen processing JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -