Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 10, 2018
- Source ID
- 10.7554/elife.34961
Entities
People
- Anita J Zaitouna
- Aviva Geretz
- Brogan Yarzabek
- Daniel S Ramon
- Eli Olson
- Gayathri N. Silva
- Jie Geng
- Malini Raghavan
- Rasmi Thomas
- Sujatha Krishnakumar
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Mayo Clinic
- National Institutes of Health
- United States Department of Defense
- University of Michigan
- Walter Reed Army Institute of Research