CD8+ T-cell mediated self-reactivity in HLA-B27 context as a consequence of dual peptide conformation.
HLA-B2709 does not predispose for Ankylosing Spondylitis although it differs from B2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles. B2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses.
Nurzia
Elisa
E
Department of Cell Biology and Development, Sapienza University of Rome, 00185 Roma, Italy.
Panimolle
Francesca
F
Cauli
Alberto
A
Mathieu
Alessandro
A
Magnacca
Adriana
A
Paladini
Fabiana
F
Sorrentino
Rosa
R
Fiorillo
Maria Teresa
MT
D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D013167:Spondylitis, Ankylosing / Q000276:immunology*
D001324:Autoantigens; D015235:HLA-B Antigens; C464936:HLA-B*27:05 antigen; C464937:HLA-B*27:09 antigen; D015796:HLA-B27 Antigen; D010455:Peptides