title: Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells.
abstract: The association of psoriasis with Streptococcus pyogenes throat infections suggests a potential antigenic target for the T cells that are known to infiltrate psoriatic skin. Streptococcal M protein share an extensive sequence homology with the human epidermal keratins. Keratin 17 (K17), while being mostly absent from uninvolved skin, is up-regulated in psoriatic lesions. Consequentially, M-protein-primed T cells may recognize up-regulated keratin epitopes via molecular mimicry. Using in vitro lymphocyte culture and cytokine flow cytometry we demonstrate that HLA-Cw*0602(+) psoriasis patients had significant CD8(+) T cell interferon (IFN)-gamma responses to peptides from the K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA(+)) subset of CD8(+) T cells. CD4(+) T cells showed only borderline responses. CLA(+) CD8(+) T cells from Cw6(+) non-psoriatic individuals responded to some M6 peptides but rarely to K17 peptides. Cw6(-) psoriasis patients showed a response that was intermediate between Cw6(+) patients and controls. These findings indicate that psoriatic individuals have CD8(+) T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M proteins and human keratins may be targets for the CD8(+) T cells that infiltrate psoriatic skin lesions.
authors.affiliation: Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland. Andrewj@landspitali.is
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.forename: J E
authors.initials: JE
authors.lastname: Gudjonsson
authors.forename: H
authors.initials: H
authors.lastname: Sigmundsdottir
authors.forename: T J
authors.initials: TJ
authors.lastname: Love
authors.forename: H
authors.initials: H
authors.lastname: Valdimarsson
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007633:Keratins / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D011565:Psoriasis / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; C063419:CTAGE1 protein, human; D002352:Carrier Proteins; D015236:HLA-C Antigens; C491620:HLA-C*06:02 antigen; D008562:Membrane Glycoproteins; D010455:Peptides; D016201:Receptors, Lymphocyte Homing; C014689:streptococcal M protein; D007633:Keratins; D007371:Interferon-gamma