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.
van Lith
Marcel
M
School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, United Kingdom.
McEwen-Smith
Rosanna M
RM
Benham
Adam M
AM
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