"2-6-11" motif in heat shock protein 60 and central nervous system antigens: a preliminary study in multiple sclerosis patients.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with unknown etiology and pathogenesis. A local autoimmune process involving activation of autoreactive T cells against CNS protein components is likely crucial in the development of MS lesions. Myelin-reactive T cells are believed to be primed in the periphery during infections by antigens of bacterial or viral origin via molecular mimicry, a postulated mechanism that might account for the trigger of an autoimmune response on the basis of sequence homology between foreign and self determinants. Immune responses to heat shock proteins (hsp) have been implicated in the initiation or progression of a number of autoimmune diseases. Hsp may function as immunodominant targets during the immune response evoked by pathogens, and theoretically a cross-reactive response to sequences shared by these immunogens and autoantigens in the CNS may contribute to the pathogenesis of MS. We examined the immune response of peripheral blood mononuclear cells (PBMNc) from MS patients and healthy subjects elicited by peptides derived from hsp60 containing a common structural motif ("2-6-11" motif) already described, which is also present in CNS putative antigens. This structural pattern consists of an apolar residue or Lys at position 2, Pro always at position 6, and Glu, Asp or Lys at residue 11. Results reported here are indicative of maturation of peripheral blood monocytes towards a differentiated CD14(+)CD16(+)DR(+) cell and release of pro-inflammatory cytokines consistent with a Th1-like pattern. These are typical features exhibited by immune cells implicated in autoimmune responses.
Ruiz-Vázquez
E
E
Dpto. de Neurología, Clínica Universitaria, Universidad de Navarra, Pamplona 31080, Spain.
de Castro
P
P
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000097:blood* / Q000737:chemistry; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D009185:Myelin Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018834:Chaperonin 60; D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D009185:Myelin Proteins; D010455:Peptides