Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 beta chain to recent onset type 1 (insulin-dependent) diabetes mellitus.
A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1 (497-513) AVTPL RIFIVPPAAEY has an 11 amino acid identity with HLA-DQw8 beta (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 beta (44-63) peptide but not with the related DQw7 beta (44-63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8 beta (49-60) reacted with the DQw8 beta (44-63) peptide and BOLF1 (496-515), but not with DQw7 beta (44-63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex beta chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30; 63%) and in sera of 20 non-diabetic control subjects (13 of 20; 65%). Sera from diabetic patients did not bind to DQw8 beta (44-63) or BOLF1 (496-515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.
Sairenji
T
T
Department of Pharmacology and Medicine, University of Massachusetts Medical School, Worcester.
Daibata
M
M
Sorli
C H
CH
Qvistbäck
H
H
Humphreys
R E
RE
Ludvigsson
J
J
Palmer
J
J
Landin-Olsson
M
M
Sundkvist
G
G
Michelsen
B
B
D000293:Adolescent; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007330:Insulin Antibodies / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D012016:Reference Values; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics*
D001323:Autoantibodies; C069498:BOLF1 protein, Human herpesvirus 4; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D007330:Insulin Antibodies; D046911:Macromolecular Substances; D009842:Oligopeptides; D014764:Viral Proteins; C024211:islet cell antibody