Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis.
Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA(165-173)) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA(165-173) and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA(165-173). The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP(276-288), which had identity at eight of the nine core amino acid residues, and T-span7(58-70), which had identity at six residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell reactivity with OspA(161-170), 6 had responses to MAWD-BP(276-288), and 3 had reactivity with T-span7(58-70), but reactivity with the self-peptides was lower than that induced by the spirochetal epitope. Thus, there remains an association between OspA(165-173) and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome. However, molecular mimicry due to sequence homology between OspA(165-173) and a human peptide seems unlikely to be the critical mechanism.
Drouin
Elise E
EE
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. edrouin@partners.org
Glickstein
Lisa
L
Kwok
William W
WW
Nepom
Gerald T
GT
Steere
Allen C
AC
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001428:Bacterial Vaccines / Q000737:chemistry / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D024881:Drug Resistance, Bacterial / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008193:Lyme Disease / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology
D000954:Antigens, Surface; D001323:Autoantibodies; D001324:Autoantigens; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D008074:Lipoproteins; C072045:OspA protein; D010455:Peptides; D012333:RNA, Messenger