HLA-DP, HLA-DQ, and HLA-DR have different requirements for invariant chain and HLA-DM.
The MHC is central to the adaptive immune response. The human MHC class II is encoded by three different isotypes, HLA-DR, -DQ, and -DP, each being highly polymorphic. In contrast to HLA-DR, the intracellular assembly and trafficking of HLA-DP molecules have not been studied extensively. However, different HLA-DP variants can be either protective or risk factors for infectious diseases (e.g. hepatitis B), immune dysfunction (e.g. berylliosis), and autoimmunity (e.g. myasthenia gravis). Here, we establish a system to analyze the chaperone requirements for HLA-DP and to compare the assembly and trafficking of HLA-DP, -DQ, and -DR directly. Unlike HLA-DR1, HLA-DQ5 and HLA-DP4 can form SDS-stable dimers supported by invariant chain (Ii) in the absence of HLA-DM. Uniquely, HLA-DP also forms dimers in the presence of HLA-DM alone. In model antigen-presenting cells, SDS-stable HLA-DP complexes are resistant to treatments that prevent formation of SDS-stable HLA-DR complexes. The unexpected properties of HLA-DP molecules may help explain why they bind to a more restricted range of peptides than other human MHC class II proteins and frequently present viral peptides.
School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, United Kingdom.
Marcel
M
van Lith
Rosanna M
RM
McEwen-Smith
Adam M
AM
Benham
D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001607:Berylliosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055503:Protein Multimerization / Q000276:immunology; D021381:Protein Transport / Q000502:physiology; D012307:Risk Factors; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D018832:Molecular Chaperones; D010455:Peptides; D014764:Viral Proteins