Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Michigan, United States; Graduate Program in Immunology, Michigan Medicine, University of Michigan, Michigan, United States
Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Michigan, United States
Aviva Geretz
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
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.
