Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM.
Atypical invariant chain (Ii) CLIP fragments (CLIP2) have been found in association with HLA-DQ2 (DQ2) purified from cell lysates. We mapped the binding register of CLIP2 (Ii 96-104) to DQ2 and found proline at the P1 position, in contrast to the canonical CLIP1 (Ii 83-101) register with methionine at P1. CLIP1/2 peptides are the predominant peptide species, even for DQ2 from HLA-DM (DM)-expressing cells. We hypothesized that DQ2-CLIP1/2 might be poor substrates for DM. We measured DM-mediated exchange of CLIP and other peptides for high-affinity indicator peptides and found it is inefficient for DQ2. DM-DQ-binding and DM chaperone effects on conformation and levels of DQ are also reduced for DQ2, compared with DQ1. We suggest that the unusual interaction of DQ2 with Ii and DM may provide a basis for the known disease associations of DQ2.
Fallang
Lars-Egil
LE
Centre for Immune Regulation and Institute of Immunology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway.
Roh
Sujin
S
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Holm
Anders
A
Centre for Immune Regulation and Institute of Immunology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway.
Bergseng
Elin
E
Centre for Immune Regulation and Institute of Immunology, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
Yoon
Taejin
T
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Fleckenstein
Burkhard
B
Centre for Immune Regulation and Institute of Immunology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway.
Bandyopadhyay
Arunima
A
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Mellins
Elizabeth D
ED
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Sollid
Ludvig M
LM
Centre for Immune Regulation and Institute of Immunology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway.|Centre for Immune Regulation and Institute of Immunology, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods; D011485:Protein Binding / Q000235:genetics / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; C045084:invariant chain