Analysis of intestinal HLA-DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.
Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.
Oshitani
Nobuhide
N
Department of Gastroenterology, Osaka City University Medical School, Osaka, Japan. nobu@med.osaka-cu.ac.jp
Hato
Fumihiko
F
Kitagawa
Seiichi
S
Maeda
Kiyoshi
K
Higuchi
Kazuhide
K
Matsumoto
Takayuki
T
Arakawa
Tetsuo
T
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001419:Bacteria / Q000302:isolation & purification; D002175:Candida / Q000302:isolation & purification; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000276:immunology / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000032:analysis; D012016:Reference Values
D006684:HLA-DR Antigens; D010446:Peptide Fragments; D010455:Peptides