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HLA-B polymorphisms and intracellular assembly modes

Malini Raghavan1, Jie Geng1

  • 1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Molecular Immunology
|August 5, 2015
PubMed

Human leukocyte antigen (HLA) class I molecules are ligands for antigen receptors of cytotoxic T cells (CTL) and inhibitory receptors of natural killer (NK) cells. The high degree of HLA class I polymorphism allows for the selection of distinct and diverse sets of antigenic peptide ligands for presentation to CTL. The extensive polymorphisms of the HLA class I genes also result in large variations in their intracellular folding and assembly characteristics. Recent findings indicate that North American HLA-B variants differ significantly in the stabilities of their peptide-deficient forms and in the requirements for the endoplasmic reticulum (ER)-resident factor tapasin for proper assembly. In HIV-infected individuals, the presence of tapasin-independent HLA-B allotypes links to more rapid progression to death. Further studies are important to better understand how the intrinsic structural characteristics of HLA class I folding intermediates affect immune responses mediated by CTL and NK cells.

Keywords:
AIDSCalreticulinERp57Endoplasmic reticulumHIVHLA-BMHC class IPeptide loading complexTAP transporterTapasin

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