Structural requirements for recognition of the HLA-Dw14 class II epitope: a key HLA determinant associated with rheumatoid arthritis.

• DOI: 10.1073/pnas.87.20.8051
• Publication Date: 2006-05-31T11:28:36Z
• Authors: A Hiraiwa; K Yamanaka; W W Kwok; E M Mickelson; S Masewicz; J A Hansen; S F Radka; G T Nepom
• Keywords: 0301 basic medicine; HLA-D Antigens; Base Sequence; T-Lymphocytes; Genes, MHC Class II; Genetic Vectors; Homozygote; Molecular Sequence Data; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Transfection; Cell Line; Arthritis, Rheumatoid; Epitopes; 03 medical and health sciences; Mutagenesis, Site-Directed; Humans; Oligonucleotide Probes

Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, documented patterns of nucleotide sequence variation among some a particular disease. For rheumatoid arthritis, in most patients shared encoding key structural element an class II polypeptide; critical interaction molecule antigenic peptides and responding T cells, suggestive direct role disease susceptibility. We describe serological cellular immunologic characteristics encoded by arthritis-associated element. Site-directed mutagenesis DRB1 gene was used define amino acids antibody T-cell recognition element, focusing on residues that distinguish alleles Dw4 Dw14 from closely related allele, Dw10, not Both gain loss epitopes were highly dependent three within discrete domain HLA-DR molecule. Recognition strongly influenced following (in order): 70 greater than 71 67. Some alloreactive clones also acid portions DR lying outside