Cross-reactivity and sequence homology between the 65-kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules.
Immunogold ultracytochemistry and Western immunoblotting showed that polyclonal antibodies against human lactoferrin bind to the highly immunogenic 65-kilodalton (kDa) heat shock protein of mycobacteria. The fast-growing mycobacterial species Mycobacterium smegmatis showed a higher density of these receptors for antilactoferrin sera than the slow-growing M. avium. Polyclonal antibodies against mycobacteria (M. bovis BCG) recognized human lactoferrin. Comparison of the amino acid sequence of lactoferrin with that of the 65-kDa protein of M. tuberculosis revealed seven instances of four amino acid sequence homology between the microbial and the human iron-binding protein. Four of these tetrapeptide sequences were also shared with the human transferrin molecule. The shared amino acid sequence KDLL was also present in the DR1, DR3, and DR4 subsets of the DR beta subregion of major histocompatibility complex (MHC) class II molecules. The molecular mimicry between the 65-kDa mycobacterial protein and the human proteins (lactoferrin, transferrin, and MHC class II molecules) offers a molecular setting for mycobacteria-associated, T-cell-dependent autoimmune disease, namely, for rheumatoid arthritis.
Aguas
A
A
Center for Experimental Cytology (INIC), University of Porto, Portugal.
Esaguy
N
N
Sunkel
C E
CE
Silva
M T
MT
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D009504:Neutrophils / Q000276:immunology; D014168:Transferrin / Q000235:genetics / Q000276:immunology
D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; D014168:Transferrin; D007781:Lactoferrin